Return of Individual Results

Purpose and Applicability

The purpose of this webpage is to provide guidance on the return of individual research results to participants. This guidance is intended to apply not only to clinical research, but also to all types of research, including genomic research and socio-behavioral research.

Context

An individual research result is any information collected, generated or discovered in the course of a research study that is linked to the identity of a research participant.

These may be results that are:

• Collected at the beginning of a study to determine if a person meets inclusion and exclusion criteria for the research
• Generated about a participant during the progress of the research
• Discovered in the course of the research that are beyond the aims of the research but have potential health or reproductive importance (often called “incidental findings”)
• Identified, collated, or interpreted after analysis of the collected data and/or results has been completed

Return of result. In general, the action of returning or sharing results with research participants should be thought of as offering the result. When individual research results are offered, participants should be given the opportunity to decide whether or not to receive the results, rather than automatically receiving them. Legal reporting requirements, such as mandated reporting of communicable diseases, abuse, and intent to harm to self or others, represent an exception. There may rarely be some results of critical and immediate clinical importance that require the fiduciary duty of the participant’s health care provider (when the researcher is also the health care provider) to take precedence over the patient’s preference.

Researcher Responsibilities

Researchers must provide the IRB with a plan for any return of individual results. The return of results may be a part of the planned study objectives or may be limited to circumstances in which the return is indicated. The plan should discuss which results will be offered if any, the method of return, and the conditions under which results will be returned. The responsibility to return results ends with the end of funding for the research or, when there is no funding, completion of the study objectives.

IRB Responsibilities

It is the responsibility of the IRB to:

• Ensure that researchers have a plan for results that should be offered for return and returned based on the decision-making framework described below ^[5]
• Assess any plans that the researchers may have to return other types of results and determine if the return should be permitted based on the decision-making framework and criteria for IRB approval
• Review all plans for return of results to determine if the risk of returning the results is reasonable in relation to the anticipated benefit
• Review the consent process to determine if the consent model and information provided to participants about the results and conditions of return are appropriate, including the ability to opt out of return of non-critical results
• Review the disclosure process to determine if risks to participants have been minimized

Decision-Making Framework

The table below describes which results should be offered to research participants and the recommended timing of the return depending upon the study purpose and the result return plan. Standardized definitions of included terminology are provided below the table.

Nature of Result	Decision	Timing*
Clinically actionable, valid and urgent	Return result	Within 7 days
Clinically actionable, valid and non-urgent	Return if feasible	Researcher discretion
Other results	Researcher discretion	Researcher discretion
*Note: Clinically actionable, valid and urgent results should be returned within 7 days of discovery but may need to be returned sooner or later depending upon the circumstances. Otherwise, the timing is generally at the discretion of the researcher. When applicable, timing of return should be guided by clinical judgment to ensure that participants are able to receive any necessary medical care and should take into account the possible impact on the validity of the study through introduction of bias. Definitions Clinically actionable: There are established therapeutic or preventive interventions or other available actions that have the potential to change the clinical course of the disease/condition or lead to an improved health outcome. Urgent: The results pose life-threatening or severe health consequences if not treated or addressed quickly. Valid: The results are analytically and clinically valid. Analytic validity indicates how accurately and reliably the test measures a certain criterion, such as a genotype of interest. Clinical validity refers to the accuracy at predicting a clinical outcome. Feasible: The return of results can be reasonably accomplished without compromising the research. Feasibility is determined by multiple factors including potential for causing bias, the resources available to communicate the results effectively and appropriately, as well as other challenges, costs and burdens. For example, returning results to a low income, transient population with mental health disorder may not be feasible if the study does not have the significant resources that would be required to put an appropriate plan in place.

Results that should be returned. Every effort should be made to offer results that are clinically actionable, valid and urgent because there is a clear benefit to the return and to not return the result could lead to harm to the participant (even though the harm does not arise directly from research activities). Examples: very high calcium levels, highly elevated liver function test results, positive results for reportable STDs.

Results that are clinically actionable and non-urgent should be offered to participants unless the return of those results is not feasible and taking into consideration the timing of the return. Examples: BRCA1 pathogenic variant, a mildly elevated cholesterol level or modestly elevated liver function test, a systolic blood pressure that is in the upper limit of normal, a slow but steady increase in blood chemistry values.

Other results. Researchers have the discretion to choose to offer other results to participants. Examples: non-actionable genetic results, clinical test results in the normal range, experimental and/or uncertain results. In these circumstances, the IRB will determine whether their return should be permitted according to IRB criteria for approval. This decision is made by assessing whether the risks to participants have been minimized by the disclosure plan and whether the risks of return are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result. In making this assessment the IRB takes into consideration the validity of the result, feasibility, timing of the return and potential costs to participants, and risks associated with the return of the results such as misuse or misunderstanding of the information, psychological stress, and impact on family relationships.

Exceptions. The IRB may approve exceptions to the requirements of this framework on a case-by-case basis after careful consideration of the risks and benefits as described above. A possible exception could occur if the IRB were to determine that the return of certain clinically actionable, valid and non-urgent would be detrimental to the study participants even if it is feasible to return the result. For example, providing a clinical diagnosis could become a safety concern for emotionally distressed participants with various mental health conditions. Another possible exception could be that the IRB identifies results that do not fit the definition of clinically actionable and yet are important to the well-being of the participants.

Assessing Validity

A result’s reliability and analytic and clinical validity are important considerations in deciding whether to return a research result. Results lacking analytical validity may be inaccurate and misleading. If the clinical validity is not established, the meaning of the result will not be clear, raising questions about how, or whether, the result should be returned. Poor reliability may mean the return of “false positive” or “false negative” results.

In a healthcare context, the reliability and validity of a test or diagnosis conducted using devices or assays is usually indicated by regulatory approval from the Food and Drug Administration (FDA) or certification under the Clinical Laboratory Improvement Amendment (CLIA) from the Centers for Medicare and Medicaid Services (CMS). However, there a variety of ways to demonstrate reliability and validity. The IRB will consider evidence of validity such as studies demonstrating diagnostic, prognostic, or predictive value, use of confirmatory testing, and quality management systems. The IRB may also obtain consultations from subject matter experts as needed.

Results that are not validated, not of high reliability, and not actionable carry the least justification for provision to subjects for reasons of direct clinical benefit. Researchers are therefore discouraged from returning:

• Results that are likely to be misinterpreted
• Results that have limited benefit to participants and would entail significant burden (cost or complexity) to return whose return is not a requirement to meet study aims
• Results without established clinical validity for a life-threatening or sensitive health condition
• Results for which there are serious questions regarding validity, reliability, or identity

Laboratory Certification and Return of Results

Certification requirement. Federal regulations called the Clinical Laboratory Improvement Amendment (CLIA) require certification of facilities that perform any tests on “materials derived from the human body for the purpose of providing information for the diagnosis, prevention, or treatment of any disease or impairment of, or the assessment of the health of, human beings.” The purpose of the certification is to ensure the accuracy, reliability, and timeliness of results from clinical laboratories. Many states (including Washington State) have their own laboratory certification program which is a legally acceptable substitute for CLIA certification.

Applicability to research. The federal agency that oversees CLIA describes ^[13] applicability of the CLIA regulations to the return of individual research results as follows: “Research testing where patient-specific results are reported from the laboratory, and those results will be or could be used ‘for the diagnosis, prevention, or treatment of any disease or impairment of, or the assessment of the health of, human beings’ is presumed to be subject to CLIA absent evidence to the contrary.” This means that if a research laboratory intends to report individual-level results to the tested individual or their clinician, the lab must first obtain CLIA certification, or establish a process to obtain confirmatory testing in a CLIA-certified lab. IRB approval for returning results may be withheld in the absence of CLIA certifications.

How to obtain CLIA certification. When necessary, CLIA certification can be obtained through one of the following:

• The CLIA program with more information at this link ^[14].
• The Washington State laboratory licensing program (through the State Department of Health) with more information at this link ^[15].

Consent

Information about informed consent when providing research results can be found in the guidance on Designing the Consent Process ^[16].

Communication of Results

Meaning and limitations. The communication of each type of result returned should be done in a way that facilitates participant understanding of the meaning and limitations of the results. In general, this communication should provide a written summary of the results, including a clear explanation about whether or not the results are clinically actionable and what is known or unknown about the meaning of the result. It should also include any reference information that might be needed to help the participant understand the result, such as standard reference ranges, comparative risks, or categorization of information. It is important to keep in mind that providing reference information is not the same as providing personalized interpretation or clinical guidance, and participants should be referred for follow-up care or consultation when appropriate.

As participants may not understand the degree to which the research results can have substantially greater uncertainties than clinical results, it may be necessary to include a warning statement for results that are prone to misinterpretation or misuse. This is particularly important for a result that may be confused with an established clinical test. For example, the written summary might include a statement warning participants that the level of risk is still unknown and that no actions to reduce risk are known. Researchers might also choose to include information about plans for future research to study these questions.

Communication methods. Research results can be returned through a variety of communication methods that are matched to participant needs, preferences and the context of the research. The communication approach needs to be considered on a case-by-case basis because of differences in study objectives, study design, characteristics of the study population, types of results to be returned, expertise, resources, and infrastructure. In many circumstances, a multimodal approach to returning results will be beneficial.

The table below lays out the advantages and disadvantages of some commonly used communication methods for returning individual research results.

Method	Context	Advantages and Disadvantages
In-person meeting	Study that has ongoing contact with participant, study site resources are available and contact information is up-to-date.	Advantages: Maximizes the ability to provide clarification, answer participant questions, assess and address potential confusion from the participant. Disadvantages: There is a considerable time and resource commitment, and potential challenges in reaching individual study participants and scheduling them to meet with a clinical research physician, staff member or specialist. In some cases, resources are needed to provide specialized expertise, such as a genetic counselor. This method is not well suited to scenarios where results to be returned are time-sensitive.
Phone/video-conference	Participants are not able to travel to receive information in person, or study site resources are no longer available.	Advantages: Provides many of the advantages of an in-person meeting, but is less personal. This method can be carried out quickly if the return is time-sensitive and the participant must be reached promptly. Disadvantages: There is still a considerable time and resource commitment and the potential challenges in reaching individual study participants by phone.
Electronic delivery (secure website, patient portal, email)	Participants have access to the Internet and it is possible to leverage existing or emerging health technologies.	Advantages: Allows data to be downloaded or transferred between researchers and participants at any time, without scheduling appointments. This method is useful for large-scale communications and can be enhanced with tools, such as video, to deliver a consistent and thorough message and be available on demand. Once established, online access is time and resource efficient and can provide participants with more ownership of their healthcare and results. Disadvantages: The investment needed to design, maintain and secure the Internet portal. Security and identity management provisions must be considered. Online access to information does not address the participant’s need to ask questions. This method is problematic for participants who have no Internet access, have limited health literacy, or technology proficiency.
Confidential letter	A confidential way of sharing results with participants.	Advantages: This method does not involve the time and resource commitment of an in-person meeting. The participant can refer to this written information at any time and is able to share the results accurately with health care providers. Disadvantages:: It does not address the participant’s need to ask questions and have results explained. Additional safeguards may be needed to protect privacy with regard to their participation in the study (e.g., no identifying return address on the outside envelope).
Medical record	HIPAA gives participants the right to access results that become part of the designated record set (although access can be deferred until study completion).	Advantages: Costs and resources associated with returning the result are avoided. The participant is spared the decision about whether to receive the results and can pursue this later. Disadvantages: The results may not be meaningful to the participant without interpretation. Services for interpretation of the data may not be widely available or may be costly. The participant may not become aware of medically significant information.

Regulatory References

• SACHRP Recommendations, “Return of Individual Results”, 2016
• National Academies of Sciences, Engineering, and Medicine, “Returning Individual Research Results to Participants: Guidance for a New Research Paradigm”. The National Academies Press 2018
• Multi-Regional Clinical Trials Center of Brigham and Women’s hospital and Harvard University, “MRCT Center Recommendations Document for Returning Individual Results”, 2017
• Jarvik et al., “Return of genomic results to research participants: The floor, the ceiling, and the choices in between”. American Journal of Human Genetics 94(6): 818-826. 2014

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Keywords: Results