Conrad V. Fernandez

Ethical and Practical Guidelines for Reporting Genetic Research Results to Study Participants: Updated Guidelines From a National Heart, Lung, and Blood Institute Working Group

In January 2009, the National Heart, Lung, and Blood Institute convened a 28-member multidisciplinary Working Group to update the recommendations of a 2004 National Heart, Lung, and Blood Institute Working Group focused on Guidelines to the Return of Genetic Research Results. Changes in the genetic and societal landscape over the intervening 5 years raise multiple questions and challenges. The group noted the complex issues arising from the fact that technological and bioinformatic progress has made it possible to obtain considerable information on individuals that would not have been possible a decade ago. Although unable to reach consensus on a number of issues, the working group produced 5 recommendations. The working group offers 2 recommendations addressing the criteria necessary to determine when genetic results should and may be returned to study participants, respectively. In addition, it suggests that a time limit be established to limit the duration of obligation of investigators to return genetic research results. The group recommends the creation of a central body, or bodies, to provide guidance on when genetic research results are associated with sufficient risk and have established clinical utility to justify their return to study participants. The final recommendation urges investigators to engage the broader community when dealing with identifiable communities to advise them on the return of aggregate and individual research results. Creation of an entity charged to provide guidance to institutional review boards, investigators, research institutions, and research sponsors would provide rigorous review of available data, promote standardization of study policies regarding return of genetic research results, and enable investigators and study participants to clarify and share expectations for the handling of this increasingly valuable information with appropriate respect for the rights and needs of participants.

Considerations and Costs of Disclosing Study Findings to Research Participants

The disclosure of study findings to participants in research reflects the moral obligation of researchers, founded in the ethical principle of respect for human dignity, to avoid treating human participants as a means to an end. Human dignity is respected through proper procedures of obtaining

Providing Research Results to Participants: Attitudes and Needs of Adolescents and Parents of Children With Cancer

PURPOSEnThere is an increasing demand for researchers to provide research results to participants. Our aim was to define an appropriate process for this, based on needs and attitudes of participants.nnnMETHODSnA multicenter survey in five sites in the United States and Canada was offered to parents of children with cancer and adolescents with cancer. Respondents indicated their preferred mode of communication of research results with respect to implications; timing, provider, and content of the results; reasons for and against providing results; and barriers to providing results.nnnRESULTSnFour hundred nine parents (including 19 of deceased children) and 86 adolescents responded. Most parents (n = 385; 94.2%) felt that they had a strong right to research results. For positive results, most wanted a letter or e-mail summary (n = 238; 58.2%) or a phone call followed by a letter (n = 100; 24.4%). If the results were negative, phone call (n = 136; 33.3%) or personal visits (n = 150; 36.7%) were preferred. Parents wanted the summary to include long-term sequelae and suggestions for participants (n = 341; 83.4%), effect on future treatments (n = 341; 83.4%), and subsequent research steps (n = 284; 69.5%). Understanding the researcher was a main concern about receiving results (n = 145; 35.5%). Parents felt that results provide information to support quality of life (n = 315; 77%) and raise public awareness of research (n = 282; 68.9%). Adolescents identified similar preferences.nnnCONCLUSIONnParents of children with cancer and adolescents with cancer feel strongly that they have a right to be offered research results and have specific preferences of how and what information should be communicated.

Offering to Return Results to Research Participants: Attitudes and Needs of Principal Investigators in the Children's Oncology Group

Purpose The offer to return a summary of results to participants after the conclusion of clinical research has many potential benefits. The authors determined current practice and attitudes and needs of researchers in establishing programs to return results to research participants. Methods An Internet survey of all 236 principal investigators (PIs) of the Childrens Oncology Group in May 2002 recorded PI and institutional demographics, current practice, and perceived barriers to and needs of PIs for the creation of research results programs. Results One hundred fifty (63.8%) PIs responded. Few institutions (n = 5) had established, comprehensive programs to offer the return of results. PIs indicated that major impediments to the implementation of such programs are the preparation of lay summaries, time constraints, the task of contacting participants, and potential distress for the participants. PIs identified the following facilitators to the establishment of a program in their own institution: lay summaries, web site, preparation of an oncologists summary, and financial credits. There was no clear consensus as to when the results should be shared: 30% indicated after the study was closed and 24% indicated at the time of publication of results. A substantial proportion of respondents opposed or strongly opposed the implementation of a universal offering of results to research participants. Conclusions Few Childrens Oncology Group institutions have programs that offer the return of results to research participants. Significant barriers and facilitators to this process have been identified.

Informing research participants of research results: analysis of Canadian university based research ethics board policies

Background: Despite potential benefits of the return of research results to research participants, the TriCouncil Policy Statement (TCPS), which reflects Canadian regulatory ethical requirements, does not require this. The policies of Canadian research ethics boards (REBs) are unknown. Objectives: To examine the policies of Canadian university based REBs regarding returning results to research participants, and to ascertain if the presence/absence of a policy may be influenced by REB member composition. Design: Email survey of the coordinators of Canadian university based REBs to determine the presence/absence of a policy on return of research results to research participants both during an ongoing study and at conclusion. REB coordinators were asked to return a copy of the policy or guidelines and to describe the member composition of their REB. Findings: Of 50 REBs that were contacted 34 (68%) responded and 22 (64.7%) met the inclusion criteria. Two (9.1%) had a policy that governed the return of research results while on a study, and seven (31.8%) following the completion of a study. Presence of an ethicist or a lawyer on the REB did not influence the presence/absence of such policies. No REBs had specific guidelines describing how participants should be informed of results. Conclusions: Most REBs did not require researchers to disclose study results to research participants either during or following a study. Thus this study identifies an ethical shortcoming in the conduct of human research in Canada. It has also demonstrated that there are no clear recommendations by REBs to facilitate the return of results to participants following research projects.

Returning incidental findings from genetic research to children: views of parents of children affected by rare diseases

Purpose To explore parental perceptions and experiences regarding the return of genomic incidental research findings in children with rare diseases. Methods Parents of children affected by various rare diseases were invited to participate in focus groups or individual telephone interviews in Montreal and Ottawa. Fifteen participants were interviewed and transcriptions were analysed using thematic analysis. Results Four emergent themes underscored parental enthusiasm for receiving incidental findings concerning their childs health: (1) right to information; (2) perceived benefits and risks; (3) communication practicalities: who, when, and how; and (4) service needs to promote the communication of incidental findings. Parents believed they should be made aware of all results pertaining to their childs health status, and that they are responsible for transmitting this information to their child, irrespective of disease severity. Despite potential negative consequences, respondents generally perceived a favourable risk-benefit ratio in receiving all incidental findings. Conclusions Understanding how parents assess the risks and benefits of returning incidental findings is essential to genomic research applications in paediatric medicine. The authors believe the study findings will contribute to establishing future best practices, although further research is needed to evaluate the impact of parental decisions on themselves and their child.

Attitudes of parents toward the return of targeted and incidental genomic research findings in children.

Purpose:We describe parental attitudes toward the return of targeted and incidental genomic research results in the setting of high-risk pediatric cancer and inherited childhood diseases.Methods:A validated 36-item questionnaire was mailed to participants in three large-scale genome research consortia examining attitudes toward receipt of genomic research results and the influence of certainty, severity, and onset of the condition, in addition to responsibilities to extended family and provision of results even after death of the proband.Results:Of the 563 participants who were sent questionnaires, 362 (64%) responded. Most of them stated a positive right to receive results related to the target condition (97%) or to incidental findings (86%); no difference was found in results between participants with cancer and those with orphan diseases. Furthermore, 92% indicated that genomic research for childhood-onset conditions should occur. The majority wanted incidental results predicting susceptibility even to untreatable fatal conditions (83%), to multiple conditions (87%), or to those with uncertain impact (70%). Most felt sibling genomic results showing serious conditions, whether treatable (93%) or not (88%), and/or results discovered after death of the proband should be shared with family (74%).Conclusion:Many parents of children in pediatric genomic research indicated a strong desire to receive a broader range of results than is described in consensus recommendations. Clear delineation of what will be offered should be established at the time of consent.Genet Med 16 8, 633–640.Genetics in Medicine (2014); 16 8, 633–640. doi:10.1038/gim.2013.201

Returning a Research Participant's Genomic Results to Relatives: Analysis and Recommendations

Genomic research results and incidental findings with health implications for a research participant are of potential interest not only to the participant, but also to the participants family. Yet investigators lack guidance on return of results to relatives, including after the participants death. In this paper, a national working group offers consensus analysis and recommendations, including an ethical framework to guide investigators in managing this challenging issue, before and after the participants death.

Disclosing Secondary Findings from Pediatric Sequencing to Families: Considering the “Benefit to Families”

Secondary findings for adult-onset diseases in pediatric clinical sequencing can benefit parents or other family members. In the absence of data showing harm, it is ethically reasonable for parents to request such information, because in other types of medical decision-making, they are often given discretion unless their decisions clearly harm the child. Some parents might not want this information because it could distract them from focusing on the childs underlying condition that prompted sequencing. Collecting family impact data may improve future policy determinations.

Ethical and Practical Guidelines for Reporting Genetic Research Results to Study Participants

In January 2009, the National Heart, Lung, and Blood Institute convened a 28-member multidisciplinary Working Group to update the recommendations of a 2004 National Heart, Lung, and Blood Institute Working Group focused on Guidelines to the Return of Genetic Research Results. Changes in the genetic and societal landscape over the intervening 5 years raise multiple questions and challenges. The group noted the complex issues arising from the fact that technological and bioinformatic progress has made it possible to obtain considerable information on individuals that would not have been possible a decade ago. Although unable to reach consensus on a number of issues, the working group produced 5 recommendations. The working group offers 2 recommendations addressing the criteria necessary to determine when genetic results should and may be returned to study participants, respectively. In addition, it suggests that a time limit be established to limit the duration of obligation of investigators to return genetic research results. The group recommends the creation of a central body, or bodies, to provide guidance on when genetic research results are associated with sufficient risk and have established clinical utility to justify their return to study participants. The final recommendation urges investigators to engage the broader community when dealing with identifiable communities to advise them on the return of aggregate and individual research results. Creation of an entity charged to provide guidance to institutional review boards, investigators, research institutions, and research sponsors would provide rigorous review of available data, promote standardization of study policies regarding return of genetic research results, and enable investigators and study participants to clarify and share expectations for the handling of this increasingly valuable information with appropriate respect for the rights and needs of participants.