Reporting Results References
Informed consent for population-based research involving genetics.
Beskow, L. M. and Burke, W. and Merz, J. F. and Barr, P. A. (2001)
JAMA :2315-2321. PubMed »
A multidisciplinary group put together by the Centers for Disease Control makes suggestions for a revised and updated participant consent form to be used in genetic research, primarily concerning population-based research of lower penetrance gene variants. The group argues that this modified informed consent form should include a number of sections, which are meant to offer the participants important information that will hopefully contribute to their decision whether or not to participate in the study (i.e., Why is this study being done? What is involved? What are the risks? How will I find out about the results of the study?). The committee also agreed against giving individual genetic results to participants in population-based research involving low penetrance gene variants, the reasons for which are elaborated upon in the article. Also included in this paper are a newly created consent form and an informational brochure for the prospective research subjects.
Discovery and disclosure of incidental findings in neuroimaging research.
Illes, J. and Kirschen, M. P. and Karetsky, K. and Kelly, M. and Saha, A. and Desmond, J. E. and Raffin, T. A. and Glover, G. H. and Atlas, S. W. (2004)
Journal of Magnetic Resonance Imaging :743-747.
DOI:10.1002/jmri.20180 PubMed » Full Text »
An NIH-sponsored working group put forth ten recommendations addressing incidental findings (IFs) in neuroimaging research. The ten recommendations are as follows: researchers should anticipate the potential for IFs and establish a process to handle them, include a professional competent to interpret for clinically significant findings, have communication with the subject or surrogate be through a qualified member of the research team, facilitate verbal communication in a timely way and document in writing, address IFs in consent forms, IRBs should address IFs in review, IFs may not be relevant for some modalities, guidelines should highlight researcher responsibility but not stand in the way of research, and that the development of a database of IFs would be valuable.
Disclosure of genetic information obtained through research.
Quaid, K. A. and Jessup, N. M and Meslin, E. M (2004)
Genetic testing :347-355. PubMed »
The authors provide an overview of current regulations on disclosure to subjects, relatives of subjects, and about former subjects who are now deceased. They conclude that current regulations do not adequately deal with the familial nature of genetic research, do not discuss relatives to the subject, and do not protect the deceased.
Guidance on Research Involving Coded Private Information or Biological Specimens.
Department of Health and Human Services (Office for Human Research Protections) (2004) Full Text »
The document provides guidance on when research involving coded private information or human biological specimens does not qualify as research involving human subjects. It also reaffirms OHRP policy that in some cases, research involving only coded private information or specimens is not human subjects research. It distinguishes between research involving coded private information or specimens that does not involve human subjects and human subjects research that is exempt from the requirements of HHS regulations. According to 45 CFR.46.102(d) of HHS regulations, "research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalize knowledge. Activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes." According to 45 CFR 46.102(f), "Human subject means a living individual about whom an investigator conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information.
Working Group on Reporting Genetic Results in Research Studies Meeting Summary.
National Heart, Lung and Blood Institute (2004) Full Text »
This NHLBI working group, consisting of experts from the fields of ethics, law and scientific, medical and public health communities, came together to discuss and form recommendations as to what type of information should be released to research subjects, how and when such information should be given, and what guidelines should be followed for disclosure. The group agreed on three definite conditions under which research subjects should receive their personal information from the study if that information was desired: 1) The risk for the disease should be significant, 2) the disease should have important health implications, i.e., fatal or substantial morbidity or reproductive implications, and 3) proven therapeutic or preventative interventions should be available. The working group set forth guidelines for reporting genetic results to individual research participants in the areas of analytic validity, clinical validity and clinical utility, as well as ethical, legal and social issues. The group also stressed the need for "formal, uniform guidance for IRBs, institutions, investigators and sponsors with respect to best practices for testing and reporting genetic results in human research studies."
IRB Guidebook: Chapter on Human Genetics Research, Draft 2.
NHRPAC Working Group on Genetics (2002) Full Text »
In 2002, the National Human Research Protections (NHRPAC) Working Group put forward recommendations regarding the regulations of human subjects research, including subject access to data. They recommended that this issue be dealt with as part of the consent process.
Research Involving Human Biological Materials: Ethical Issues and Policy Guidance.
National Bioethics Advisory Commission (1999) Full Text »
Members of the National Bioethics Advisory Commission outline three recommendations concerning when and how research results should be given to subjects. First, they suggest IRBs should develop general guidelines for the disclosure of the results of research to subjects and require investigators to address these issues explicitly in their research plans. Such disclosure should only occur when all of the following apply: a) The findings are scientifically valid and confirmed, b) the findings have significant implications for the subject's health concerns, and c) a course of action to ameliorate or treat these concerns is readily available. Second, the investigator in his or her research protocol should describe anticipated research findings and circumstances that might lead to a decision to disclose the findings to a subject, as well as a plan for how to manage such a disclosure. And third, when research results are disclosed to a subject, appropriate medical advice or referral should be provided.
Reporting Results to Individual Participants
Offering to Return Results to Research Participants: Attitudes and Needs of Principal Investigators in the Children?s Oncology Group.
Fernandez, C. V. and Kodish, E. and Shurin, S. and Weijer, C. (2003)
Journal of Pediatric Hematology/Oncology :9. PubMed »
Few researchers return results to research participants. In a study of PIs in the Children's Oncology Group, barriers to returning results include: preparation of lay summaries, time constraints, task to contacting participants, and distress of participants.
Informing study participants of research results: an ethical imperative.
Fernandez, C. V. and Kodish, E. and Weijer, C. (2003)
IRB :12-19. PubMed »
In this paper, Fernandez, Kodish and Weijer explore what they believe to be an ethical obligation of researchers to provide research results to study participants once that information is available. They argue that despite whether a participant chooses to receive information or not, respect for each participant binds researchers to at least make the results accessible and understandable to those from whom data was collected. They also argue that there are specific guidelines to be followed concerning the details of how and when such information should be provided as well as preparation for the impact, both psychological and physical, the information may have on participants. All such details must be addressed in order to fully respect the dignity of the individual: an obligation these authors view with utmost importance considering the necessity of their participation in the progress of scientific research.
Considerations and costs of disclosing study findings to research participants.
Fernandez, C. V. and Skedgel, C. and Weijer, C. (2004)
DOI:10.1503/cmaj.1031668 PubMed » Full Text »
This paper explores the level and nature of resources that would be needed to return research results to participants. The reasons for returning results and the factors that would influence delivery of this information, such as cost and complexity, are summarized for both researchers and for funding agencies.
Research in human genetics: the tension between doing no harm and personal autonomy.
Pelias, M. K. (2005)
Clinical Genetics :1-5.
DOI:10.1111/j.1399-0004.2004.00324.x PubMed » Full Text »
This article includes a historical perspective on the researcher-subject relationship, discusses current and emerging issues around genetic research and reporting issues, identifies key questions around the reporting of results, and offers a sample informed consent form for the reporting of results.
Returning Genetic Research Results to Individuals: Points to Consider.
Renegar, G. and Webster, C.J. and Stuerzebecher, S. and Harty, L. and Ide, S. and Balkite, B. and Rogalski-Salter, T. and Cohen, N. and Spear, B. and Barnes, D. and Brazell, C. (2006)
DOI:10.1111/j.1467-8519.2006.00473.x Full Text »
The Pharmacogenetics Working Group, an association of researchers in pharmaceutical companies, discuss points to consider in returning genetic research results generated in clinical drug development trials. The authors provide an overview of international and national policies and regulations, offer different considerations for risks and benefits to subjects (medical information, clinical relevance, privacy and confidentiality, competency), and offer suggestions for dealing with reporting results in study design, coding processes, informed consent, and results presentation.
Disclosing individual results of clinical research: implications of respect for participants.
Shalowitz, D. I. and Miller, F. G. (2005)
JAMA :737-40. PubMed » Full Text »
The authors argue that in most cases, research results should be disclosed to subjects, based on the ethical principle of respect for persons.
Unexpected findings in identifiable stored blood samples after analysis without consent: moral arguments for and against disclosure.
Verweij, M. F. and Hamel, B. C. J. (2002)
Genetic Counseling :115-121. PubMed »
The article presents a case where a pathogenic mutation was found in a blood sample used in a second study without prior consent. The article discusses moral arguments for and against informing the research participant which includes of discussion medical, psychological and financial impact of disclosure or non-disclosure. The article concludes that researchers should obtain consent before using identifiable stored samples in further studies.
Informed Consent and Reporting Results
Disclosure of the right of research participants to receive research results.
Fernandez, C. V. and Kodish, E. and Taweel, S. and Shurin, S. and Weijer, C. (2003)
DOI:10.1002/cncr.11391 PubMed » Full Text »
This study analyzed consent forms from 2 acute lymphoblastic leukemia studies of 235 institutional members of the Children's Oncology Group and concluded that few IRB-approved consent forms disclose the right of participants to receive research results and fewer explicitly indicate how and when those results could be provided to the participants.
Genetic research involving human biological materials: a need to tailor current consent forms.
Hull, S. C. and Gooding, H. and Klein, A. P. and Warshauer-Baker, E. and Metosky, S. and Wilfond, B. S. (2004)
IRB :1-7. PubMed »
In this study, the researchers analyze the content of consent forms to determine what information subjects were being given about the use of their biological samples in genetic research. The study found that consent forms examined often had serious omissions, irrelevant inclusions and considerable variability depending on the specific IRB. Consent forms often followed a mechanical format for genetic studies based on recommendations and did not consider the specificities of the research project. The study recommended better tailoring consent forms to fit the informational needs of a potential subject.
Ethical issues in genetic research: disclosure and informed consent.
Reilly, P. R. and Boshar, M. F. and Holtzman, S. H. (1997)
Nature Genetics :16-20.
DOI:10.1038/ng0197-16 PubMed »
This article discusses key dimensions for disclosure and consent regarding genetic research, including: description of the nature of the study, description of the research terms, privacy guidelines, archiving, distribution and other uses of subject DNA, development of commercial products, other sensitive biological information, and consequences of the findings of the study.
Reporting Results of Clinical Trials
What must research subjects be told regarding the results of completed randomized trials?.
Markman, M. (2004)
IRB :8-10. PubMed »
Markman discusses the potential ethical conflicts and issues that emerge around what research subjects should be told about completed randomized trial results by focusing on a particular case study involving an ovarian cancer therapy in a Phase III trial. During the trial, an interim analysis of the data revealed that 50% of the research subjects had a highly statistically significant improvement under one particular treatment. The DSMC elected to close the trial and inform participants of results. Because the study was closed, the initial research question was not definitely answered, and hence this particular treatment, Markman believes, should not become the standard of care. She questions how the results of the study should be interpreted because of the lack of definitive knowledge about whether the treatment works, and identifies six issues that emerge about future clinical trials. First, do the results of the trial mandate that all research subjects in ongoing and future research trials be informed of this outcome? Second, should it be up to the patient or physician-investigator to make a decision, and what does that say about the physician-investigator/subject relationship? If a physician-investigator does not inform a patient about the results, but enters her into a new clinical trial that does not include the particular treatment with provisional results, does the investigator have a conflict of interest? Who should decide what to tell research subjects about trial results and what should be the criteria for making that decision? Is it critical to inquire if there are alternative study designs that would permit the therapy in question, but allow for evaluation of new drugs as well? What role should the IRB play?
Do patients participating in clinical trials want to know study results?.
Partridge, A. H. and Burstein, H. J. and Gelman, R. S. and Marcom, P. K. and Winer, E. P. (2003)
Journal of the National Cancer Institute :491-492. PubMed »
The authors developed a questionnaire for breast cancer patients involved in clinical trials in order to see whether the participants wanted to know the results of the trial. They found that the vast majority of patients did want to know the results of the trial, and that they felt it should be their doctor that revealed their study results.
Clinical Context (including Duty to Warn, Duty to Recontact)
Duty to warn at-risk relatives for genetic disease: Genetic counselors' clinical experience.
Dugan, R. B. and Wiesner, G. L. and Juengst, E. T. and O'Riordan, M. and Matthews, A. L. and Robin, N. H. (2003)
American Journal of Medical Genetics Part C: Seminars in Medical Genetics :27-34.
DOI:10.1002/ajmg.c.10005 PubMed » Full Text »
This study interviewed genetic counselors on their own experience in situations where a patient with a genetic disease refused to notify at-risk relatives. The study showed that the majority of genetic counselors believe that they have an ethical obligation to inform at-risk relatives of patients. However, less than 10% responded that they would actually disclose information to relatives. Out of 119 counselors, only one had ever revealed information without a patient's consent. Overwhelmingly, genetic counselors respected patient confidentiality.
Medical Geneticists' duty to warn at-risk relatives for genetic disease.
Falk, M. J. and Dugan, R. B. and O'Riordan, M. A. and Matthews, A. L. and Robin, N. H. (2003)
American Journal of Medical Genetics Part A :374-380.
DOI:10.1002/ajmg.a.20227 PubMed » Full Text »
This study surveyed medical geneticists on situations where a patient with a genetic disease refused to notify at-risk relatives. This was a follow-up study to an earlier study on the experiences of genetic counselors. In this study, only 1% of geneticists disclosed information to relatives without consent. Eighty percent who did not warn, cited patient confidentiality, the physician-patient relationship, eventual case resolution by other means and legal liability as factors in their decision.
The duty to recontact: attitudes of genetics service providers.
Fitzpatrick, J. L. and Hahn, C. and Costa, T. and Huggins, M. J. (1999)
American Journal of Human Genetics :852-860. PubMed » Full Text »
The authors conducted a study of Genetic Service Provider (GSP) attitudes toward the duty to recontact patients about research advances. GSPs are divided on whether the duty to recontact should be the standard of care, and those who see patients are less likely to believe that it should.
Ethical, legal, and practical concerns about recontacting patients to inform them of new information: the case in medical genetics.
Hunter, A. G. and Sharpe, N. and Mullen, M. and Meschino, W. S. (2001)
American Journal of Medical Genetics :265-276.
DOI:10.1002/ajmg.1568 PubMed » Full Text »
This article looks at the ethics of the "duty to recontact," including the potential influence of legal precedent. Additionally, the article discusses functional and resource implications if the duty to recontact were adopted as the standard of care.
Disclosure of familial genetic information: perceptions of the duty to inform.
Lehmann, L. S. and Weeks, J. C. and Klar, N. and Biener, L. and Garber, J. E. (2000)
The American Journal of Medicine :705-711.
DOI:10.1016/S0002-9343(00)00594-5 PubMed »
This study explored the views of 200 Jewish women in Boston on whether at-risk relatives of a patient with a genetic disease should be informed. The results show that nearly all the women felt that the patient should voluntarily inform family members. However, less than 25% of women felt that the physician should inform relatives against the wishes of the patient. Therefore, according to the participants of the survey, disclosure of genetic results was the patient's responsibility and not the physician's obligation.
The "duty to warn" a patient's family members about hereditary disease risks.
Offit, K. and Groeger, E. and Turner, S. and Wadsworth, E. A. and Weiser, M. A. (2004)
JAMA :1469-1473. PubMed »
This article discusses a physician's duty to warn from three perspectives: legal, regulatory, and professional. In addition, the authors present considerations for clinicians to weigh (autonomy versus beneficence.)
Concern for families and individuals in clinical genetics.
Parker, M. and Lucassen, A. (2003)
J Med Ethics :70-73.
DOI:10.1136/jme.29.2.70 PubMed » Full Text »
This article discusses the ethical tensions between concern for families and concern for individuals in clinical genetics and describes cases which illustrate those ethical tensions.
Legal Issues with Reporting of Results
Misusing informed consent: a critique of limitations on research subjects' access to genetic research results.
Banks, T. M. (2000)
Saskatchewan Law Review :539-580. PubMed »
In this article, the author argues that the current system of informed consent that usually denies subjects access to research results has evolved to limit the obligations of researchers to their subjects while claiming to inform and protect subjects. The author believes that medical researchers have an obligation, based on the law of fiduciaries in Canada, to provide the choice to subjects to be recontacted with research results.
Genetic test results and the duty to disclose: can medical researchers control liability?.
Furman, R. L. (1999)
Seattle University Law Review :391-429. PubMed »
This article discusses the duties of physicians and researchers to disclose genetic test results and forecasts what the future of the duty to disclose may look like depending on whether courts adopt theories of tort, property, or contract relating to the researcher-subject relationship.
Genetic testing and human subjects in research.
Laidlaw, S. A. and Raffel, L. J. and Daar, J. F. (2002)
Whittier Law Review :429-472. PubMed »
In a 2002 Health Law Symposium, these three scholars discussed issues related to genetic testing and human subjects in research, and in particular addressed the issue of disclosure of research results.
Genetic risk: the new frontier for the duty to warn.
Petrila, J. (2001)
Behavioral Sciences and the Law :405-421.
DOI:10.1002/bsl.449 PubMed » Full Text » This article discusses the evolution of the legal duty to warn in genetics related cases, ramifications of these cases for health care decision-making, and application of the duty to warn to mental health practice.
Subjects' Attitudes Toward the Reporting of Individual Research Results
Informing subjects of epidemiologic study results.
Bunin, G. R. and Kazak, A. E. and Mitelman, O. (1996)
Pediatrics :486. PubMed »
Researchers administered surveys to parents who participated in an epidemiologic study of pediatric brain tumors in order to research public experiences of research participation and getting research results. Researchers found that participants did not seem to have any negative effects from getting research results, and see getting results as valuable.
Disclosure of research results to research participants: focus group and questionnaire development examining attitudes of participants.
Fernandez, C. V. (2003)
Researchers conducted a focus group and interviews with participants in an oncology study, and found that participants felt that the return of research results would be helpful, and that participants should be responsible for retaining contact with researchers after the study is over.
Informing clinical trial participants about study results.
Partridge, A. and Winer, E. (2002)
JAMA :363-365. PubMed » Full Text »
This article discusses benefits of providing clinical trial participants research results, and also looks at barriers to doing so.
Reactions of participants to the results of a randomised controlled trial: exploratory study.
Snowdon, C. and Garcia, J. and Elbourne, D. (1998)
BMJ :21-26. PubMed » Full Text » The authors of the articles conducted interviews with parents of babies who participated in a neonatal clinical trial in order to research their reactions to getting results. Researchers found that participants thought that other participants should get access to the results, and while some experienced distress, they still felt it was important to know the results.
Public Perceptions of the Collection of Human Biological Samples, Summary Report.
Wellcome Trust and Medical Research Council (2000) Full Text »
Accompanying the development of the UK Biobank was a large public consultation program that consisted of national focus groups soliciting public attitudes and concerns about genetic research, including individual feedback of research results.
Primary care physicians' perceptions of barriers to genetic testing and their willingness to participate in research.
Mountcastle-Shah, E. and Holtzman, N. A. (2000)
American Journal of Medical Genetics :409-416.
DOI:10.1002/1096-8628 PubMed » Full Text »
Ethical issues in newborn screening research: lessons from the Wisconsin cystic fibrosis trial.
Taylor, H. A. and Wilfond, B. S. and Taylor, B. S. (2004)
The Journal of Pediatrics :292-296. PubMed »