Return of Research Results or Incidental Research Findings

This guidance applies to research that may generate results or incidental findings that may significantly affect the health of the participants or their families. This includes but is not limited to research involving:

• Genetic testing;
• Imaging - such as MRI scans, CT scans, PET scans, and X-rays. Specifically high high-density images that provide anatomic or physiological data of the type that is used in clinical diagnosis or treatment;
• Other procedures for which there is a probability that the results or procedures could identify results or incidental findings that would meet the criteria outlined in the next question.

In general, if the research participant can be identified by the bank or the PI, research results/incidental findings that meet all of the criteria listed below should be returned unless the participant states that he/she does not want to know the results or unless the Institutional Review Board (IRB) has approved a written request for not returning results or incidental findings.

Individual results/incidental findings should be offered to study participants if they meet ALL of the following criteria:

1. The finding has important health implications for the participant, and the associated risks are established and substantial.
2. The finding is actionable, that is, there are established therapeutic or preventive interventions or other available actions that have the potential to change the clinical course of the disease.
3. The test is analytically valid, or in the case of imaging, qualified professionals interpret the scan, and the disclosure plan complies with all applicable laws.
4. The informed consent used to collect the tissue/specimen/data informed the participants that results may be returned, or the participant opted to receive his or her individual results. (Fabsitz et al., 2010)

For clinical purposes, the American College of Medical Genetics and Genomics Working Group determined a “minimum list” of DNA variants in 57 genes for 37 conditions for which findings in a clinical setting should be reported if the data are readable. This guidance serves as a useful guideline for determining if a gene is actionable. (American College of Medical Genetics and Genomics et al., 2013)

Other sources of guidance may be available in the future.

The research findings or image should be reviewed by a qualified reviewer (e.g., board-certified radiologists or qualified physicians). Any images or reports of those images that become part of a research participant’s medical record should be considered to be of clinical quality. The American College of Radiology (ACR) Practice Guidelines and Technical Standards describe recommended training, skills, and techniques for specific areas of clinical practice.

• For laboratory results, Clinical Laboratory Improvement Amendments (CLIA) is the only mechanism available, as there are no other current equivalent validating associations or certifications.
• If tests are performed in a non-CLIA-approved laboratory, such as a research laboratory, and it has been determined that one of the findings needs to be returned to the participant based on the criteria in Question 2, the PI must confirm the specific result in question (e.g., sequencing) in a CLIA-approved lab before the finding is returned to the participant.
• For an overview of how CLIA applies to the return of research results, see the Department of Health and Human Services recommendations.

Yes. If the result identified has met all criteria, except for “analytical validity”, the IRB expects that results should be returned AFTER the result is clinically verified. Otherwise, justification should be submitted to the IRB for why clinical verification is not ethically appropriate or practicably possible, and therefore, the results will not be returned. 

If no clinically accepted standard exists for validating the result, the result should not be returned to the participant. 

Ideally, the obligation should extend through active use of the specimens for research. At a minimum, the obligation should extend through the availability of study funding. (Fabsitz et al., 2010)

The Presidential Commission for the Study of Bioethical Issues has published recommendations in this area. Because whole genome sequencing can reveal potentially clinically important information that may have implications for the participant and descendants, concerns are heightened. Participants may not anticipate the type of access or variety of uses unless they are adequately informed. Informed consent language or ancillary educational materials should address the issues and potential privacy safeguards.

Given the current controversy and confusion regarding what researchers should or should not do when faced with incidental findings, coupled with the unique relationship that exists between Investigator and participant (i.e., as opposed to clinician to patient), researchers do not have a duty or ethical obligation to actively look for incidental findings, even if the “raw” sequence data is available.

Ideally, a comprehensive disclosure plan would be submitted as part of the initial IRB application. The IRB application should include the following:

• Description of results that may be returned;
• Name of the individual who will have the authority to determine whether the research results or incidental findings meet the criteria outlined in Question 2;
• Qualifications of the individual identified to return the results to the participant;
• Timing regarding when the results will be returned;
• Mode of communication to be used;
• Plans for pre- and post-counseling for the participant, if appropriate;
• If the participant is a minor or an individual of diminished consent capacity, description of to whom the findings will be returned (see Question 14);
• Description of plans for allowing participants to withdraw (see Question 12);
• Description of plans for sharing samples with other investigators, if applicable (see Question 17);
• Requests for Waiver of Informed Consent/Authorization, if applicable;
• A description of the consent process and a copy of the form, which should include a section on returning of research results and incidental findings (see Question 13); and
• HIPAA Authorization form, if applicable.

Yes, procedures must be addressed in the informed consent and the IRB application.

Specify in the informed consent that the participant may withdraw their specimen and associated data from future analysis and reporting. The withdrawal would not apply to data analyzed prior to the receipt of the participant’s request to withdraw samples from the bank or PI use.

For a complete list of IRB expectations and suggested template language, go to the Repository/Bank/ Registry Informed Consent/ Authorization webpage.

Issues to address specific to the return of results include:

• Inform participants regarding what results or incidental findings will be offered to participants.
• Indicate if findings will be reviewed to determine if appropriate to return.
• Define incidental findings, if applicable.
• Inform participants if results will not be provided and explain why.
• If findings are to be disclosed, describe disclosure procedures (e.g., genetic counseling).
• If findings are to be disclosed, explain the implications of making results or incidental findings available.
• Allow participants to opt in or out of receiving results in the future or indicate if participants will be contacted and offered a “result-specific” consent describing implications or ramifications of receiving a result that has been found.

If the study/bank meets these three conditions: a) designed to include minors; b) identifiers will be maintained; and c) it is possible that the minors could reach the age of majority before the study ends or while the bank still has the specimen, the IRB application should describe the procedures for making a reasonable attempt to contact the individual to consent at the age of majority. 

If the bank has made the effort, but a portion of the participants were not successfully contacted, the bank could request the IRB to approve a waiver of informed consent based on criteria in 45 CFR 46.116(d) for the participants that could not be reached.

Researchers/Banks should submit an Unanticipated Problem report to the IRB, which addresses: 

• Recommendation regarding whether the finding meets IRB criteria outlined in Question 2;
• Also, the disclosure plan, which includes elements listed in Question 11. 

Yes, the American College of Medical Genetics and Genomics (ACMG) recommends that all clinical molecular genetic test results be reviewed and interpreted by an individual certified in either Clinical Molecular Genetics (ABMG) or Molecular Genetic Pathology (ABPath/ABMG). The professional interpretation of test results should be provided by an individual certified in Clinical Genetics (ABMG), Clinical Cytogenics (ABMG), Clinical Molecular Genetics (ABMG), or Molecular Genetic Pathology (ABPath/ABMG). (American College of Medical Genetics and Genomics et al., 2013)

• The IRB application should include a description of the procedures for sharing samples.
• The secondary user is generally prohibited from making efforts to re-identify the individual donor who provided the material.
• The specimen/ data may be transferred; however, the responsibility to return results remains with the UK researcher.
• The specimen/data are transferred to the secondary user only after the secondary user agrees in writing to abide by the UK guidance on return of research results.  
• A Material Transfer Agreement (MTA) should be used to detail the responsibilities of the recipient investigator, including agreement not to re-identify the donor and plans to notify the UK PI regarding research results or incidental findings, as defined in the IRB-approved protocol should be used. MTA information is available on the OTC Material Transfers, Non-Disclosure, Data Use Agreements and Confidential Disclosures webpage.
• The participant donor should be informed of the possibility for secondary use of the specimens; ideally, when the specimen is initially collected. Otherwise, the IRB would need to determine if the donor(s) would need to be contacted and re-consented. 

The UK PI should submit a Modification Request to the IRB describing the plan to share specimens/data, plan for handling of incidental findings or research results, re-contact, and re-consent.  (See Questions 11, 13, and 17)

If the data obtained from the medical records contain any of the 18 HIPAA identifiers, HIPAA requirements for research do apply.

Yes. The federal Office for Human Research Protections (OHRP) considers activities that exist for the express purpose of research to be in the scope of human research requiring IRB review. 

To banks or repositories that provide human-derived specimens and/or data for research purposes.

The IRB application for a bank/repository protocol may include, but is not limited to, the following:

• Purpose and scope;
• Description of material (type, leftover, limitations, etc);
• Procedures for collecting, transmitting, storing, and sharing of material;
• Safeguards to protect privacy and confidentiality of donors (honest-broker, data-security, firewalls, software programs for separating information from identifiers, coding, encryption, limited access, confidentiality agreements, see the National Cancer Institute (NCI) Best Practices for Biospecimen Resources);
• Process for review of requests to access specimens/data;
• Plan for who will determine if secondary research meets the federal definition of human research requiring IRB review;
• Investigator agreements or terms of Material Transfer Agreement (MTA), if required;
• Informed Consent and, if applicable, Authorization Process;
• Policy and procedure for participants’ withdrawal of material;
• Policy and procedure for return of research results;
• Existence and purpose of advisory committee, if applicable; and
• Plan for the destruction or transfer of material should the repository close.

See the University of Kentucky (UK) Office of Research Integrity (ORI) Research Biospecimen Bank Guidance and Research Registry Guidance for more information. 

The amount of detail to be included in this section of the bank/repository consent depends in part upon the bank/repository's proposed consent process (including conditions, timing, expertise of the individual obtaining consent, etc.) and the bank’s IRB-approved standard operating procedures for returning research results or incidental findings.

If the individuals obtaining informed consent at the time of collection have the expertise needed to explain the complex ramifications of returning the results, then the consent process and form should include detailed information and give the participant the opportunity to indicate whether or not they want to receive results.  Sample “opt in” or “opt out” language can be found at the Repository/Bank/ Registry Informed Consent/ Authorization webpage.

On the other hand, if the individual obtaining consent does not have the appropriate expertise to explain the potential implications, the offer to allow the participant to “opt in” or “opt out” of receiving a result or finding could be deferred. The consent form and process would include a brief explanation informing participants that they may be contacted if information becomes available that the researchers believe they should know.  If a subsequent finding or result is ‘deemed’ returnable, a detailed informed consent would then be obtained, allowing the participant to “opt in” or “opt out” of receiving the results or incidental finding. This expanded consent process and form would include the ramifications of returning the results or incidental findings. The results or incidental consent form would need prior IRB review and approval and would be submitted to the IRB as an amendment (Modification Request) to the existing IRB-approved protocol.

Actionable -The following description of "actionable results" is taken from the NHLBI working group paper (Circ Cardiovasc Genet 2010), "...finding is actionable, that is, there is established therapeutic or preventative interventions or other available actions that have the potential to change the clinical course of the disease [or provide important pharmacogenetic information that is likely to impact future care].”

Biospecimen - A quantity of tissue, blood, urine, or other human-derived material.  Portions or aliquots of a biospecimen are referred to as samples (NCI Best Practices working definition).

Directly identifiable specimen is labeled with personal identifiers; for example, name, medical record number, social security number, laboratory accession number, or any elements of dates except dates limited to year alone. Any of the 18 personal identifiers specified under HIPAA constitutes a personal identifier.

Incidental finding – a finding concerning an individual research participant that has potential health or reproductive importance and is discovered in the course of conducting research but is beyond the aims of the study (Wolf SM, et al. Managing Incidental Findings in Human Participants Research: Analysis and Recommendations. Journal of Law, Medicine & Ethics. 2008;36(2):219–248)

Indirectly identifiable specimen- retains a link (or code) to identifiable information about the donor.

Research Bank or Repository- an entity involved in procuring, processing, storing and/or distributing material (tissue/specimens/data) expressly for use in research. 

Allyse M and Michie M. Not-so-incidental findings: the ACMG recommendations on the reporting of incidental findings in clinical whole genome and whole exome sequencing. Trends Biotechnol. 2013 May 3. pii: S0167-7799(13)00092-9. doi: 10.1016/j.tibtech.2013.04.006. Web. 25 June 2013.

American Academy of Pediatrics. “Policy Statement: Ethical and Policy Issues in Genetic Testing and Screening of Children”. Pediatrics (2013) 131(3); 620-622. doi: 10.1542/peds.2012-3680. Web 22 October 2018. 

American College of Medical Genetics and Genomics (ACMG). “Policy Statement: Points to consider in the clinical application of genomic sequencing”. Genet Med. 2012 August; 14(8): 759-761. doi:10.1030/gim.2012.74. Web. 22 October 2018.

Jonathan S. Berg, Michael Adams, Nassib Nassar, Chris Bizon, Kristy Lee, Charles P. Schmitt, Kirk C. Wilhelmsen, and James P. Evans. An informatics approach to analyzing the incidentalome. Genet Med. 2013 January; 15(1): 36–44. doi:10.1038/gim.2012.112. Web. 21 June 2013.

Jonathan S. Berg, MD, PhD, Laura M. Amendola, MS, Christine Eng, MD, Eliezer Van Allen, MD, Stacy W. Gray, MD, AM, Nikhil Wagle, MD, Heidi L. Rehm, PhD, Elizabeth T. DeChene, MS, Matthew C. Dulik, PhD, Fuki M. Hisama, MD, Wylie Burke, MD, PhD, Nancy B. Spinner, PhD, Levi Garraway, MD, PhD, Robert C. Green, MD, MPH, Sharon Plon, MD, PhD, James P. Evans, MD, PhD and Gail P. Jarvik, MD, PhD and the members of the CSER Actionability and Return of Results Working Group. “Processes and preliminary outputs for identification of actionable genes as incidental findings in genomic sequence data in the Clinical Sequencing Exploratory Research Consortium”, Genet Med  November 2013; 15: 860-867 Web 14 November 2013

Centers for Disease Control (CDC)

Laura M. Beskow; Wylie Burke; Jon F. Merz; et al. “Informed Consent for Population-Based Research Involving Genetics”. JAMA. 2001;286(18):2315-2321 (doi:10.1001/jama.286.18.2315). Web. 21 June 2013.

Biesecker, Leslie G., Wylie Burke, Isaac Kohane, Sharon E. Plon, and Ron Zimmern. "Next-generation Sequencing in the Clinic: Are We Ready?" Nature Reviews Genetics 13, 818-824 (November 2012) | doi:10.1038/nrg3357. Web. 21 June 2013.

Marianna J. Bledsoe, MA1, William E. Grizzle, MD, PhD2, Brian J. Clark, MBChB, FRCPath3, and Nikolajs Zeps, BSc, PhD4–6.“Practical implementation issues and challenges for biobanks in the return of individual research results”. Genetics in Medicine (2012) Volume: 14, Pages: 478–483 DOI: doi:10.1038/gim.2011.67. Web. 21 June 2013.

Ebony B Bookman, Aleisha A Langehorne, John H Eckfeldt, Kathleen C Glass, Gail P Jarvik, Michael Klag, Greg Koski, Arno Motulsky, Benjamin Wilfond, Teri A Manolio, Richard R Fabsitz, and Russell V Luepker. Reporting Genetic Results in Research Studies: Summary and Recommendations of an NHLBI Working Group. Am J Med Genet A. 2006 May 15; 140(10): 1033–1040. doi:  10.1002/ajmg.a.31195 Web. 24 June 2013.

Annelien L. Bredenoord, Martine C. de Vries & Johannes J. M. van Delden. “Next-generation sequencing: does the next generation still have a right to an open future?” Nature Reviews Genetics Volume: 14, Page: 306 Year published:(2013) DOI:doi:10.1038/nrg3459. Web. 21 June 2013.

Wylie Burke MD, PhD, Armand H. Matheny Antommaria MD, PhD, Robin Bennett MS, CGC, Jeffrey Botkin MD, MPH, Ellen Wright Clayton MD, JD, Gail E. Henderson PhD, Ingrid A. Holm MD, MPH, Gail P. Jarvik MD, PhD, Muin J. Khoury MD, PhD, Bartha Maria Knoppers JD, PhD, Nancy A. Press PhD, Lainie Friedman Ross MD, PhD, Mark A. Rothstein JD, Howard Saal MD, Wendy R. Uhlmann MS, CGC, Benjamin Wilfond MD, Susan M. Wolf JD & Ron Zimmern FRCP, FFPHM, “Recommendations for returning genomic incidental findings? We need to talk!” Genetics in Medicine (01 August 2013) Published online 2013 Aug 1. doi: 10.1038/gim.2013.113. Web 22 October 2018 

Caulfield T, McGuire AL, Cho M, Buchanan JA, Burgess MM, et al. (2008) Research ethics recommendations for whole-genome research: Consensus statement. PLoS Biol 6(3): e73. doi:10.1371/journal.pbio.0060073. Web. 21 June 2013. http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060073 

Ellen Wright Clayton JD, MD, Susanne Haga PhD, Patricia Kuszler JD, MD, Emily Bane MPH, Krysta Shutske MPH, & Wylie Burke MD, PhD. Managing incidental genomic findings: legal obligations of clinicians. Genetics in Medicine (February 2013), DOI: doi:10.1038/gim.2013.7

Ellen Wright Clayton MD, JD & Susan E. Kelly PhD  “Let us ask better questions”, Genetics in Medicine (23 May 2013) 15, Pages: 871–872 DOI: doi:10.1038/gim.2013.68

David W. Craig, Robert Goor, Zhenyan Wang, Justin Paschall, Jis Ostell, Mike Feolo, Stephen T. Sherry, and Teri A. Manolio. Assessing and Managing Risk when Sharing Aggregate Genetic Variant Data. Nature Reviews Genetics 12, 730-736 (October 2011) doi:10.1038/nrg3067. Web. 19 August 2013.

Gillian Crawford MSc, BA(Hons), Nicola Foulds PhD, MRCP, Angela Fenwick PhD, MA, Nina Hallowell DPhil, MA & Anneke Lucassen DPhil (Oxon), FRCP “Genetic medicine and incidental findings: it is more complicated than deciding whether to disclose or not.” Genetics in Medicine 03 October 2013 Volume: 15, Pages: 896–899 DOI: doi:10.1038/gim.2013.165 Web 14 November 2013

Dressler, L. G., Smolek, S., Ponsaran, M. A., Markey, J. M., Starks, H., Gerson, N., Lewis, S., Press, N., Juengst, E., Wiesner, G. L. (2012, February). IRB Perspectives on the Return of Individual Results from Genetic Research. Genet. Med. 14(52), 215-222. Web. 25 June 2013.

Evans, James P. “Return of results to the families of children in genomic sequencing: tallying risks and benefits.” Genetics in Medicine 15, 435-436 June 2013 doi:10.1038/gim.2013.54 Web. 10 September 2013.

James P. Evans, MD, PhD “Finding Common Ground.” Genetics in Medicine. 17 October 2013, 15, Pages: 852–853 DOI: doi:10.1038/gim.2013.150 Web 14 November 2013

National Heart, Lung, and Blood Institute (NHLBI)

Fabsitz RR, McGuire A, Sharp RR, et al. Ethical and practical guidelines for reporting genetic research results to study participants: updated guidelines from an NHLBI working group. Ciro Cardiovasc Genet 2010; 3:574-580. Web 24 June 2013.

Stephanie M. Fullerton, DPhil, Wendy A. Wolf, PhD, Kyle B. Brothers, MD, Ellen Wright Clayton, MD, JD, Dana C. Crawford, PhD, Joshua C. Denny, MD, Philip Greenland, MD, Barbara A. Koenig, PhD, Kathleen A. Leppig, MD, Noralane M. Lindor, MD, Catherine A. McCarty, PhD, MPH, Amy L. McGuire, JD, PhD, Eugenia R. McPeek Hinz, MD, Daniel B. Mirel, PhD, Erin M. Ramos, PhD, MPH, Marylyn D. Ritchie, PhD, MS, Maureen E. Smith, MS, CGC, Carol J. Waudby, MS, Wylie Burke, MD, PhD and Gail P. Jarvik, MD, PhD. Return of individual research results from genome-wide association studies: experience of the Electronic Medical Records and Genomics (eMERGE) Network. Genet Med 2012:14(4):424–431. doi: 10.1038/gim.2012.15 Web 22 October 2018.

Amy S Gargis, Lisa Kalman, Meredith W Berry, David P Bick, David P Dimmock, Tina Hambuch, Fei Lu, Elaine Lyon, Karl V Voelkerding, Barbara A Zehnbauer, Richa Agarwala, Sarah F Bennett, Bin Chen, Ephrem L H Chin, John G Compton, Soma Das, Daniel H Farkas, Matthew J Ferber, Birgit H Funke, Manohar R Furtado, Lilia M Ganova-Raeva, Ute Geigenmüller, Sandra J Gunselman, Madhuri R Hegde, Philip L F Johnson et al. “Assuring the quality of next-generation sequencing in clinical laboratory practice.” Nature Biotechnology 30, 1033–1036 (2012) doi:10.1038/nbt.2403. Web. 21 June 2013.

Catherine Gliwa & Benjamin E. Berkman (2013): Do Researchers Have an Obligation to Actively Look for Genetic Incidental Findings?, The American Journal of Bioethics, 13:2, 32-42 Web. 25 June 2013. 

Green RC, Berg JS, Berry GT, Biesecker LG, Dimmock DP, Evans JP, Grody WW, Hegde MR, Kalia S, Korf BR, Krantz I, McGuire AL, Miller DT, Murray MF, Nussbaum RL, Plon SE, Rehm HL, Jacob HJ. “Exploring concordance and discordance for return of incidental findings from clinical sequencing.” Genet Med. 2012 Apr:14(4):405-10. doi: 10.1038/gim.2012.21. Epub 2012 Mar 15. Web. 21 June 2013.

Robert C. Green, MD, MPH, Jonathan S. Berg, MD, PhD, Wayne W. Grody, MD, PhD, Sarah S. Kalia, ScM, CGC, Bruce R. Korf, MD, PhD, Christa L. Martin, PhD, FACMG, Amy McGuire, JD, PhD, Robert L. Nussbaum, MD, Julianne M. O’Daniel, MS, CGC, Kelly E. Ormond, MS, CGC, Heidi L. Rehm, PhD, FACMG, Michael S. Watson, MS, PhD, FACMG, Marc S. Williams, MD, FACMG, Leslie G. Biesecker, MD. ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing. American College of Medical Genetics and Genomics. March 19, 2013 Web. 21 June 2013.

Kristien Hens, Carla E Van El, Pascal Borry, Anne Cambon-Thomsen, Martina C Cornel, Francesca Forzano, Anneke Lucassen, Christine Patch, Lisbeth Tranebjaerg, Eric Vermeulen, Elena Salvaterra, Aad Tibben and Kris Dierickx on behalf of the PPPC of the European Society of Human Genetics13. Developing a policy for paediatric biobanks: principles for good practice. European Journal of Human Genetics (2013) 21, 2–7. Web. 21 June 2013.

IRB Advisor. (2012, December). Report balances privacy versus whole genome sequencing: Misuse of information is addressed. Vol. 12, No. 12. Pages 133-135.

Johnston, JJ, Rubinstein WS, Facio FM, Nq D, Singh LN, Teer JK, Mullikin JC, Biesecker LG. Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. Am J Hum Genet. 2012 Jul 13;91(1):97-108. doi: 10.1016/j.ajhg.2012.05.021. Epub 2012 Jun 14. Web. 26 June 2013. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397257/

Jennifer Klima, Sara M. Fitzgerald-Butt, Kelly J. Kelleher, Deena J. Chisolm, R. Dawn Comstock, Amy K. Ferketich, and Kim L. McBride. “Understanding of informed consent by parents of children enrolled in a genetic biobank.” Genetics in Medicine June 2013 1-8  Web. June 2013. doi:10.1038/gim.2013.86.

Klitzman, R., Applebaum, P.S., Chung, W. “Return of Secondary Genomic Findings vs Patient Autonomy: Implications for Medical Care.” JAMA July 24/31, 2013 310, 369-370, Web. September 2013

Klitzman R, Appelbaum PS, Fyer A, Martinez J, Buquez B, Wynn J, Waldman CR, Phelan J, Parens E, Chung WK. “Researchers' views on return of incidental genomic research results: qualitative and quantitative findings.” Genet Med. 2013 Nov;15 11):888-95. doi: 10.1038/gim.2013.87 Web 14 November 2013

Bartha Maria Knoppers, Myléne Deschénes, Ma’n H Zawati, and Anne Marie Tassé. Population studies: return of research results and incidental findings Policy Statement. European Journal of Human Genetics (2013) 21, 245–247; doi:10.1038/ejhg.2012.152. Web. 25 June 2013.

Hae Kyung Im, Eric R. Gamazon, Dan L. Nicolae, Nancy J. Cox. On Sharing Quantitative Trait GWAS Results in an Era of Multiple-omics Data and the Limits of Genomic Privacy. Am J Hum Genet. 2012 April 6; 90(4): 591–598. doi: 10.1016/j.ajhg.2012.02.008. Web. 19 August 2013.

Lee, Lisa M. "Request for Comments on Issues Related to Incidental Findings That Arise in the Clinical, Research, and Direct-To-Consumer Contexts." Federal Registers. Department of Health and Human Services, 5 June 2013. Web. 21 June 2013.

Lin, Zhen, Art B. Owen, and Russ B. Altman. "Genomic Research and Human Subject Privacy." Science. www.sciencemag.org, 9 July 2004. Web. 08 Aug. 2013.

Noralane M. Lindor MD, Kiley J. Johnson CGC, Jennifer B. McCormick PhD, MPP, Eric W. Klee PhD, Matthew J. Ferber PhD & Gianrico Farrugia MD. "Preserving personal autonomy in a genomic testing era.” Genetics in Medicine (2013) Volume: 15, Pages: 408–409 DOI: doi:10.1038/gim.2013.24. Web. 21 June 2013.

Lohn Z, Adam S, Birch P, Townsend A, Friedman J. Genetics professionals' perspectives on reporting incidental findings from clinical genome-wide sequencing. Am J Med Genet A. 2013 Mar;161(3):542-9. doi: 10.1002/ajmg.a.35794. Web 22 October 18.

Lowrance, William W., and Francis S. Collins. "Identifiability in Genomic Research." Science. Www.sciencemag.org, 3 Aug. 2007. Web. 08 Aug. 2013.

McGuire, Amy L., Steven Joffe, Barbara A. Koenig, Barbara B. Biesecker, Laurence B. McCullough, Jennifer S. Blumenthal-Barby, Timothy Caulfield, Sharon F. Terry, and Robert C. Green. "Ethics and Genomic Incidental Findings." Policy Forum 31 May 2013: 1047-048. Science - AAAS. Web. 21 June 2013.

ACMG Policy Statement

Kristin G. Monaghan, Judith Benkendorf, Athena M. Cherry,  Susan J. Gross, C. Sue Richards,  Vernon Reid Sutton,  and Michael S. Watson “Risk categorization for oversight of laboratory-developed tests for inherited conditions.” Genetics in Medicine April 2013, 1-2 Web. January 2013. doi:10.1038/gim.2012.178. Web 22 October 18.

National Bioethics Advisory Commission (NBAC)

National Bioethics Advisory Commission. Research Involving Human Biological Materials: Ethical Issues and Policy Guidance, Vol 1.  Rockville, MD, 1999. Web 22 October 2018

O’Rourke, P. Pearl (2012, October). Research Results – To Return or not to return: That is the Question! Regional Human Subject Protection Conference presentation, Covington, KY.

Ossorio, Pilar. “Taking aims seriously: repository research and limits on the duty to return individual research findings.” Genet Med 2012:14(4):461–466.

Parker, Lisa S. “Rethinking Respect for Persons Enrolled in Research.” ASBH Exchange 9:2 (Spring 2006)

Presidential Commission for the Study of Bioethical Issues. (2012, October). Privacy and Progress in Whole Genome Sequencing. Washington, DC.

Presidential Commission for the Study of Bioethical Issues.  (2013, December). ANTICIPATE AND COMMUNICATE Ethical Management of Incidental and Secondary Findings in the Clinical, Research, and Direct-to-Consumer Contexts. Washington, DC.

Rachel B. Ramoni DMD, ScD, Amy L. McGuire JD, PhD, Jill Oliver Robinson MA, Debra S. Morley PhD, Sharon E. Plon MD, PhD & Steven Joffe MD, MPH. “Experiences and attitudes of genome investigators regarding return of individual genetic test results.” Genetics in Medicine (2013) doi:10.1038/gim.2013.58. Web. 21 June 2013.

Sanderson, SC. “Genome Sequencing for Healthy Individuals.” Trends in Genetics (2013) 29, 556-558 Web. September 2013.

Caroline Savage Bennette MPH, Susan Brown Trinidad MA, Stephanie M. Fullerton DPhil, Donald Patrick PhD, Laura Amendola MS, Wylie Burke MD, PhD, Fuki M. Hisama MD, Gail P. Jarvik MD, PhD, Dean A. Regier PhD, & David L. Veenstra PharmD, PhD “Return of incidental findings in genomic medicine: measuring what patients value—development of an instrument to measure preferences for information from next-generation testing (IMPRINT).” Genetics in Medicine (30 May 2013). Web 22 October 18.

J. V. Selby, H. M. Krumholz, R. E. Kuntz, F. S. Collins, Network News: Powering Clinical Research. Sci. Transl. Med. 5, 182fs13 (2013). doi: 10.1126/scitranslmed.3006298. Web 22 October 18.

Christian M. Simon, Janet K. Williams, Laura Shinkunas, Debra Brandt, Sandra Daack-Hirsch, and Martha Driessnack. Informed Consent and Genomic Incidental Findings: IRB Chair Perspectives. Journal of Empirical Research on Human Research Ethics: An International Journal (December 2011) 6(4), 53-67. Web. 25 June 2013.

Skirton, H.; Goldsmith, L.; Jackson, L.; O’Connor, L. A. "Direct to Consumer Genetic Testing: a Systematic Review of Position Statements, Policies and Recommendations." Obstetrical & Gynecological Survey. 68(1):20-22, January 2013. doi: 10.1097/01.ogx.0000426487.89924.fa. Web 22 October 18.

Van Ness, Brian. Genomic Research and Incidental Findings. J Law Med Ethics. 2008; 36(2): 292–212. doi:  10.1111/j.1748-720X.2008.00272.x Web. 25 June 2013.

Effy Vayena PhD & John Tasioulas DPhil, “Genetic incidental findings: autonomy regained?” Genetics in Medicine 01 August 2013 Volume:15, Pages:868–870 DOI:doi:10.1038/gim.2013.104 Web 14 November 2013.

Susan M. Wolf, Frances P. Lawrenz, Charles A. Nelson, Jeffrey P. Kahn, Mildred K. Cho, Ellen Wright Clayton, Joel G. Fletcher, Michael K. Georgieff, Dale Hammerschmidt, Kathy Hudson, Judy Illes, Vivek Kapur, Moira A. Keane, Barbara A. Koenig, Bonnie S. LeRoy, Elizabeth G. McFarland, Jordan Paradise, Lisa S. Parker, Sharon F. Terry, Brian Van Ness, and Benjamin S. Wilfond. Managing Incidental Findings in Human Subjects Research: Analysis and Recommendations. J Law Med Ethics. 2008; 36(2): 219–211. doi:10.1111/j.1748-720X.2008.00266.x. Web. 21 June 2013.

Wolf SM, Crock BN, Van Ness B, Lawrenz F, Kahn JP, Beskow LM, Cho MK, Christman MF, Green RC, Hall R, Illes J, Keane M, Knoppers BM, Koenig BA, Kohane IS, Leroy B, Maschke KJ, McGeveran W, Ossorio P, Parker LS, Petersen GM, Richardson HS, Scott JA, Terry SF, Wilfond BS, Wolf WA. Managing incidental findings and research results in genomic research involving biobanks and archived data sets. Genet Med. 2012;14:361–384. doi: 10.1038/gim.2012.23. Web. 21 June 2013. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597341/ 

Wolf, SM. “Patient Autonomy and Incidental Findings in Clinical Genomics”. Science May 2013 340, 1049-1050. Web. June 2013.

Incidental Findings from IMAGING – References

Columbia University. Institutional Review Board Policy: Incidental Findings from Imaging Procedures Conducted for Research Studies. August 2012 Web. 21 June 2013.

Johns Hopkins Medicine. Plans for Detecting and Managing Incidental Findings Associated with Research Imaging Procedures.” August 2010, Web. 21 June 2013.

Lawrence Leung. “Incidental Findings in Neuroimaging: Ethical and Medicolegal Considerations.” Neuroscience Journal Volume 2013, Article ID 439145, 7 pages. Web. 21 June 2013.

Detection and Disclosure of Incidental Findings in Neuroimaging Research. Proc. of 2005 NINDS Workshop and Conference, Bethesda, Maryland. Web. 21 June 2013.

You are being contacted by (the X bank, your primary/clinical care provider, a medical specialist, a genetic counselor) to inform you about a result or incidental finding discovered, based on your (previous) participation in a (research study or research specimen bank). An incidental finding is an unforeseen finding discovered during the course of the research, but it does not have anything to do with the goals of the research.

Generally, tests done for research purposes are not meant to provide clinical information. Researchers who receive your de-identified (specimen/information) from a specimen bank typically do not know who donated the (specimen/information). However, in the event that a researcher discovers a finding they believe may be important for the health of a donor or the donor’s family, he/she contacts the bank.

The bank has a special committee that meets to assess the findings to determine if it is in your best interest to contact you. The committee bases its determination on a number of criteria, including how accurate the test is that identified the result/finding, if a valid test exists to confirm the result/finding, and if there are actions that may be taken based on the result/finding.

If the committee decides that you should be contacted, the authorized bank staff who has access to the code that links specimens to their donor re-identifies the specimen so that you may be contacted and offered the opportunity to receive the result/finding.

It is important to remember that (scans, procedures, tests) done for research are not meant or designed to diagnose or provide clinical information. Therefore, (we have had the test repeated in a clinical laboratory, OR if you choose to receive the result/finding, additional clinically valid tests, interpreted by qualified clinical professionals, may be required to confirm the result/finding).

There is no guarantee that you will get any benefit from receiving the result/finding. However, receiving the result could allow you to (seek clinical care, adopt preventive practices, and/or make informed healthcare decisions).

There is a risk of distress from learning the result. There is a risk that (therapy, treatments, counseling) used to treat the result/finding will not work for you. There is always a risk that the result or finding is determined to be false. Any of these outcomes could cause you or your family emotional or psychological distress, or financial hardship. There may be risks from receiving the result/finding that are unknown at this time.

Genetic result risks (if applicable):

The results of genetic research apply to both you and your family members. In some cases, it could be used to make it harder for you to get or keep a job or insurance, or impact reproduction plans, family relationships, immigration status, or paternity suits (if applicable). Genetic information could be used in ways that could cause you or your family distress.

There is a Federal law called the Genetic Information Nondiscrimination Act (GINA). Generally, GINA makes it illegal for health insurance companies, group health plans, and most employers to discriminate against you based on your genetic information. Be aware that GINA does not protect you against discrimination by companies that sell life insurance, disability insurance, or long-term care insurance, nor does it prohibit discrimination on the basis of an already known genetic disease.

Whether or not you choose to receive the result/finding is voluntary. You will not lose any benefits or rights you would normally have if you choose not to receive the result/finding.

If you do not want to receive the result/finding, (there are no other choices except not receiving the result/finding, OR you may contact (insert contact) in the future should you change your mind and wish to re-consent to receiving the result/finding). Your decision will not affect your care.

If you choose to receive the result/finding, you will be provided with (testing to confirm, treatment, genetic counseling). (Testing to confirm, treatment, genetic counseling) will be provided at no cost to you, and/or you will be responsible for (testing to confirm, treatment, genetic counseling).

Access to information about you as part of the research has been limited to protect your confidentiality. To date, the only individuals who have seen your identifiable protected health information are those authorized by the bank consent and research authorization you signed when you donated your specimen. The research repository personnel have not, nor will they, place the result/finding in your medical record.

If you choose to receive the result/finding, (medical providers such as physicians, counselors, healthcare staff, and medical specialists) may see or have access to your identifiable protected health information as part of your clinical care. Your clinical caregivers may include the result/finding in your medical record as part of your clinical care.

If you choose not to receive the result/finding, (indicate disposition of result/finding, i.e., will be destroyed, will remain as part of the bank/repository record unless you choose to withdraw the result/finding).

We will make every effort to protect your health information, however, we are not responsible if you or your family choose to disclose your health or medical information.

You will not be charged to receive the result/finding. In addition, you will be provided with (i.e., X test to confirm the result, referral to an appropriate practitioner, one consultation visit with a genetic counselor).

If you choose to receive the result/finding, you will decide whether to proceed with further examinations, tests, and/or treatments that your primary care or specialist determines are medically reasonable and necessary. You and your insurer (Medicare or Medicaid) will bear the costs of such further exams, tests, or treatments.

You are encouraged to discuss the option of receiving the result/finding with your family and primary doctor or medical provider that you trust. Ask any questions that come to mind now. In the future, if you have questions, contact (the PI/research staff). If you have questions about your rights as a volunteer in the (X specimen bank), contact the staff in the Office of Research Integrity at the University of Kentucky between 8:00 am and 5:00 pm, Mon-Fri at 859-257-9428 or 1-866-400-9428.

You are the participant or are authorized to act on behalf of the participant. You have read this information, and you will receive a copy of this form after it is signed.

Decision to receive or refuse receipt of research result or incidental finding:

I chose to receive the result or finding after reading or having this form read to me and having my questions answered.

or

I chose NOT to receive the result or finding after reading or having this form read to me and having my questions answered.

(When developing the consent/authorization form, please format it to ensure the signature lines fall on a page containing text.)

Include lines for:

1. Signature of research subject or *research subject's legal representative & Date
2. Printed name of research subject or *research subject's legal representative & Representative's relationship to research subject
3. *(If applicable) Please explain the Representative's relationship to the subject and include a description of the Representative's authority to act on behalf of the subject:
4. Name of [authorized] person obtaining informed consent & Date
5. Signature of Principal Investigator or Sub/Co-Investigator