Ethical issues associated with HIV molecular epidemiology: a qualitative exploratory study using inductive analytic approaches.

BACKGROUND: HIV molecular epidemiology is increasingly recognized as a vital source of information for understanding HIV transmission dynamics. Despite extensive use of these data-intensive techniques in both research and public health settings, the ethical issues associated with this science have received minimal attention. As the discipline evolves, there is reasonable concern that existing ethical and legal frameworks and standards might lag behind the rapid methodological developments in this field. This is a follow-up on our earlier work that applied a predetermined analytical framework to examine the perspectives of a sample of scientists from the fields of epidemiology, public health, virology and bioethics on key ethical issues associated with HIV molecular epidemiology in HIV network research. METHODS: Fourteen in-depth interviews were conducted with scientists from the fields of molecular epidemiology, public health, virology and bioethics. Inductive analytical approaches were applied to identify key themes that emerged from the data. RESULTS: Our interviewees acknowledged the potential positive impact of molecular epidemiology in the fight against HIV. However, they were concerned that HIV phylogenetics research messages may be incorrectly interpreted if not presented at the appropriate level. There was consensus that HIV phylogenetics research presents a potential risk to privacy, but the probability and magnitude of this risk was less obvious. Although participants acknowledged the social value that could be realized from the analysis of HIV genetic sequences, there was a perceived fear that the boundaries for use of HIV sequence data were not clearly defined. CONCLUSIONS: Our findings highlight distinct ethical issues arising from HIV molecular epidemiology. As the discipline evolves and HIV sequence data become increasingly available, it is critical to ensure that ethical standards keep pace with biomedical advancements. We argue that the ethical issues raised in this study, whether real or perceived, require further conceptual and empirical examination.

Methodological challenges in European ethics approvals for a genetic epidemiology study in critically ill patients: the GenOSept experience.

BACKGROUND: During the set-up phase of an international study of genetic influences on outcomes from sepsis, we aimed to characterise potential differences in ethics approval processes and outcomes in participating European countries. METHODS: Between 2005 and 2007 of the FP6-funded international Genetics Of Sepsis and Septic Shock (GenOSept) project, we asked national coordinators to complete a structured survey of research ethic committee (REC) approval structures and processes in their countries, and linked these data to outcomes. Survey findings were reconfirmed or modified in 2017. RESULTS: Eighteen countries participated in the study, recruiting 2257 patients from 160 ICUs. National practices differed widely in terms of composition of RECs, procedures and duration of the ethics approval process. Eight (44.4%) countries used a single centralised process for approval, seven (38.9%) required approval by an ethics committee in each participating hospital, and three (16.7%) required both. Outcomes of the application process differed widely between countries because of differences in national legislation, and differed within countries because of interpretation of the ethics of conducting research in patients lacking capacity. The RECs in four countries had no lay representation. The median time from submission to final decision was 1.5 (interquartile range 1-7) months; in nine (50%) approval was received within 1 month; six took over 6 months, and in one 24 months; had all countries been able to match the most efficient approvals processes, an additional 74 months of country or institution-level recruitment would have been available. In three countries, rejection of the application by some local RECs resulted in loss of centres; and one country rejected the application outright. CONCLUSIONS: The potential benefits of the single application portal offered by the European Clinical Trials Regulation will not be realised without harmonisation of research ethics committee practices as well as national legislation.

Ethical issues in HIV phylogenetics and molecular epidemiology.

PURPOSE OF REVIEW: HIV phylogenetic and molecular epidemiology analyses are increasingly being performed with a goal of improving HIV prevention efforts. However, ethical, legal and social issues are associated with these analyses, and should be considered when performed. RECENT FINDINGS: Several working groups have recently outlined the major issues surrounding the use of molecular epidemiology for HIV prevention. First, the benefits of HIV molecular epidemiology remain unclear, and further work is needed to quantitatively demonstrate the benefits that can be expected. Second, privacy loss is an important risk, with implications of disclosure varying by the regional legal and social climate. Inferential privacy risks will increase with technological improvements in sequencing and analysis. Third, data sharing, which enhances the utility of the data, may also increase the risk of inferential privacy loss. Mitigation strategies are available to address each of these issues. SUMMARY: HIV molecular epidemiology for research and public health pose significant ethical issues that continue to evolve with improving technology, increased sampling and a changing legal and social climate. Guidance surrounding these issues needs to be developed for researchers and public health officials in an iterative and region specific manner that accounts for the potential benefits and risks of this technology.

STrengthening the Reporting of OBservational studies in Epidemiology: Molecular Epidemiology STROBE-ME. An extension of the STROBE statement.

Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change, susceptibility, and clinical outcomes are used as proxies for investigating the interactions between external and/or endogenous agents and the body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as STrengthening Reporting of Observational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology - Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE Statement implementing 9 existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE-ME recommendations are intended to complement the STROBE recommendations.

Disclosing individual CDKN2A research results to melanoma survivors: interest, impact, and demands on researchers.

BACKGROUND: Whether to return individual research results from cancer genetics studies is widely debated, but little is known about how participants respond to results disclosure or about its time and cost burdens on investigators. METHODS: We recontacted participants at one site of a multicenter genetic epidemiologic study regarding their CDKN2A gene test results and implications for melanoma risk. Interested participants were disclosed their results by telephone and followed for 3 months. RESULTS: Among 39 patients approached, 27 were successfully contacted, and 19 (70% uptake) sought results, including three with mutations. Prior to disclosure, participants endorsed numerous benefits of receiving results (mean=7.7 of 9 posed), including gaining information relevant to their children's disease risk. Mean psychological well-being scores did not change from baseline, and no decreases to melanoma prevention behaviors were noted. Fifty-nine percent of participants reported that disclosure made participation in future research more likely. Preparation for disclosure required 40 minutes and $611 per recontact attempt. An additional 78 minutes and $68 was needed to disclose results. CONCLUSION: Cancer epidemiology research participants who received their individual genetic research results showed no evidence of psychological harm or false reassurance from disclosure and expressed strong trust in the accuracy of results. Burdens to our investigators were high, but protocols may differ in their demands and disclosure may increase participants' willingness to enroll in future studies. IMPACT: Providing individual study results to cancer genetics research participants poses potential challenges for investigators, but many participants desire and respond positively to this information.

Returning individual research results: development of a cancer genetics education and risk communication protocol.

The obligations of researchers to disclose clinically and/or personally significant individual research results are highly debated, but few empirical studies have addressed this topic. We describe the development of a protocol for returning research results to participants at one site of a multicenter study of the genetic epidemiology of melanoma. Protocol development involved numerous challenges: (1) deciding whether genotype results merited disclosure; (2) achieving an appropriate format for communicating results; (3) developing education materials; (4) deciding whether to retest samples for additional laboratory validation; (5) identifying and notifying selected participants; and (6) assessing the impact of disclosure. Our experience suggests potential obstacles depending on researcher resources and the design of the parent study, but offers a process by which researchers can responsibly return individual study results and evaluate the impact of disclosure.

Ethical aspects of molecular epidemiology of cancer.

In molecular epidemiology of cancer where many studies are genetic in nature and they are done among healthy people, ethical issues require special consideration. Genetic information differs from other health care information in that it is predictive in nature, and it always involves at least family members, but in some genetically very homogeneous populations even a wider group. General discussion of the potential good and harm should be encouraged more, so that it would be possible for lay people to make informed decisions. Personal involvement of scientists in education of public, general discussion and considering their own studies from the point of view of the study subject and their family is in the end the only way to ensure that the spirit of international regulations of ethics are realized in practise.

Problematic variation in local institutional review of a multicenter genetic epidemiology study.

CONTEXT: Sequencing of the human genome provides an immense resource for studies correlating DNA variation and epidemiology. However, appropriately powered genetic epidemiology studies often require recruitment from multiple sites. OBJECTIVES: To document the burden imposed by review of multicenter studies and to determine the variability among local institutional review boards (IRBs) in the approval of a multicenter genetic epidemiology study. DESIGN: A PubMed search was performed to determine the frequency of citations of multicenter studies by 5-year intervals from 1974 through 2002. A 7-question survey was sent to all participating study centers to obtain information on frequency of IRB meetings, dates for submission and approval, use/nonuse of a specific consent form, type of review performed, types of consent forms required, preparation time, and number of changes requested by the IRB at each center. Centers also provided a copy of all consent forms they generated and IRB correspondence regarding the study. SETTING AND PARTICIPANTS: Thirty-one of 42 cystic fibrosis care centers in this single US multicenter genetic epidemiology study of cystic fibrosis replied, yielding a 74% response rate. MAIN OUTCOME MEASURES: Frequency of published research studies and consistency among IRBs. RESULTS: The number of all published single-center studies has increased 1.3-fold since 1985, while the number of published epidemiology and genetic epidemiology multicenter studies increased by 8- and 9-fold, respectively, during this same period. Evaluation of the risk of the same genetic epidemiology study by 31 IRBs ranged from minimal to high, resulting in 7 expedited reviews (23%) and 24 full reviews (77%). The number of consents required by the IRBs ranged from 1 to 4; 15 IRBs (48%) required 2 or more consents, while 10 (32%) did not require assent for children. The most common concern (52%) of IRBs pertained to the genetic aspects of the study. CONCLUSIONS: Review of a protocol for a multicenter genetic epidemiology study by local IRBs was highly variable. Lack of uniformity in the review process creates uneven human subjects protection and incurs considerable inefficiency. The need for reform, such as the proposed centralized review, is underscored by the ever increasing rate of genetic discoveries facilitated by the Human Genome Project and the unprecedented opportunity to assess the relevance of genetic variation to public health.

[Parabolic parables: predictive genetic testing, social constructions of risk, and the relation between health-care professionals and the mass media]. / Parábolas, parabólicas: testagens genéticas preditivas, construções sociais de risco e a relação profissionais da saúde/meios de comunicação de massa.

The article examines conceptual topics underlying construction of the "new public health" and epidemiology, particularly its molecular branch and the idea of genetic risk, in the face of issues raised by new technologies, globalization, today's vast increase in communication strategies, and the weakening of identity links. Problems related to the creation of new interdisciplinary fields are also considered, such as epidemiology and molecular genetics. The repercussions of the social communication of genetic contents (especially predictive genetic testing and the cloning of mammals) are also analyzed.