Empirical analysis of current approaches to incidental findings

This paper presents results found through searching publicly available U.S. data sources for information about how to handle incidental findings (IF) in human subjects research, especially in genetics and genomics research, neuroimaging research, and CT colonography research. We searched the Web sites of 14 federal agencies, 22 professional societies, and 100 universities, as well as used the search engine Google for actual consent forms that had been posted on the Internet. Our analysis of these documents showed that there is very little public guidance available for researchers as to how to deal with incidental findings. Moreover, the guidance available is not consistent.     

Understanding incidental findings in the context of genetics and genomics.

Human genetic and genomic research can yield information that may be of clinical relevance to the individuals who participate as subjects of the research. It has been common practice among researchers to notify participants during the informed consent process that no individual results will be disclosed, "incidental" or otherwise. However, as genetic information obtained in research becomes orders of magnitude more voluminous, increasingly accessible online, and more informative, this precedent may no longer be appropriate. There is not yet consensus on the responsibilities of researchers to disclose individual research results to research participants. Empirical research suggests that participants want to know individual research results. On the other hand, the increased resolution and power afforded by new genomic analyses may lead to findings of statistical, but not necessarily clinical, significance. This paper addresses the issues to be considered in deciding whether and how to disclose "incidental" findings or other findings of clinical significance that arise in the course of human genomic and genetic research. What research results should be offered, and what should not be offered? For which research should individual results be offered to research participants, when should they be offered, how, and to whom?     

Incidental findings in pediatric research

The approach to incidental research findings in children emerges by considering the child-parent relationship and balancing divergent interests and preferences. Incidental findings with clear and proximate clinical importance should be disclosed to both. We recommend that particularly sensitive or private information (e.g., pregnancy or drug use) should be disclosed to the adolescent first, while particularly serious information (e.g., cancer) should first be disclosed to the parent. These approaches allow the researcher to form an alliance with one party prior to engaging the other. However, unlike clinical settings, where there may be presumptive expectations of confidentiality about sharing information within the family, in most research settings it is reasonable to plan to disclose such information to both parties. It is important to communicate this plan during the informed consent process separately to adolescents to avoid enrolling adolescents when sensitive incidental findings such as pregnancy and drug use may be detected. The approach to incidental findings without clear and proximate benefit is challenging. Researchers should plan more limited disclosure of such incidental findings for pediatric participants than for adult participants.     

The Management of Incidental Findings in Neuro-Imaging Research: Framework and Recommendations

This paper addresses the question of how incidental findings (IFs) in clinical research should be managed by researchers, focusing in detail on IFs discovered in neuroimaging research. It begins by engaging the larger research ethics issue of whether researchers have any obligations of clinical care to participants, and assesses the content and merits of one particular framework for answering this question, Richardson and Belsky's ancillary care model. From here the paper develops an organizational structure for integrating the ancillary care model with existing research ethics standards, with the aim of better understanding their respective domains. It makes a distinction between incidental findings that are anticipated by informed consent documents, and those that are unanticipated, arguing that this distinction is critical for evaluating researcher obligations. Finally, it takes on the issue of incidental findings in neuroimaging research, translating the standards discussed into recommendations for both unanticipated and anticipated findings.     

Research malpractice and the issue of incidental findings.

Human subject research involving brain imaging is likely to reveal significant incidental findings of abnormal brain morphology. Because of this fact and because of the fiduciary relationship between researcher and subject, board-certified or board-eligible radiologists should review the scans to look for any abnormality, the scans should be conducted in accordance with standard medical practice for reviewing the clinical status of the whole brain, and the informed consent process should disclose the possibility that incidental findings may be revealed and what consequences will follow. In the event such findings are revealed, qualified physicians should explain to the subject the significance of the findings and the alternatives available.     

The law of incidental findings in human subjects research: establishing researchers' duties

Research technologies can now produce so much information that there is significant potential for incidental findings (IFs). These are findings generated in research that are beyond the aims of the study. Current law and federal regulations offer no direct guidance on how to deal with IFs in research, nor is there adequate professional or institutional guidance. We advocate a defined set of researcher duties based on law and ethics and recommend a pathway to be followed in handling IFs in research. This article traces the underlying ethical and legal theories supporting researcher duties to manage IFs, including duties to develop a plan for management in the research protocol, to discuss the possibility of and management plan for IFs in the informed consent process, and to address, evaluate, and ultimately offer to disclose IFs of potential clinical or reproductive significance to research participants when they arise.     

Big genetic data and its big data protection challenges

The use of various forms of big data have revolutionised scientific research. This includes research in the field of genetics in areas ranging from medical research to anthropology. Developments in this area have inter alia been characterised by the ability to sequence genome wide sequences (GWS) cheaply, the ability to share and combine with other forms of complimentary data and ever more powerful processing techniques that have become possible given tremendous increases in computing power. Given that many if not most of these techniques will make use of personal data it is necessary to take into account data protection law. This article looks at challenges for researchers that will be presented by the EU's General Data Protection Regulation, which will be in effect from May 2018. The very nature of research with big data in general and genetic data in particular means that in many instances compliance will be onerous, whilst in others it may even be difficult to envisage how compliance may be possible. Compliance concerns include issues relating to ‘purpose limitation’, ‘data minimisation’ and ‘storage limitation’. Other requirements, including the need to facilitate data subject rights and potentially conduct a Data Protection Impact Assessment (DPIA) may provide further complications for researchers. Further critical issues to consider include the choice of legal base: whether to opt for what is often seen as the ‘default option’ (i.e. consent) or to process under the so called ‘scientific research exception’. Each presents its own challenges (including the likely need to gain ethical approval) and opportunities that will have to be considered according to the particular context in question.     

Incidental findings and ancillary-care obligations.

Recent work on incidental findings, concentrating on the difficult problems posed by the ambiguous results often generated by high-tech medicine, has proceeded largely independently from recent work on medical researchers' ancillary-care obligations, the obligations that researchers have to deal with diseases or conditions besides the one(s) under study. This paper contends that the two topics are morally linked, and specifically that a sound understanding of ancillary-care obligations will center them on incidental findings. The paper sets out and defends an understanding of ancillary-care obligations, which is based on the idea that when participants signed up for a study they may -- independently of their beliefs and expectations and of those of the researchers -- be taken to have partially entrusted certain aspects of their health into the researchers' hands. This partial entrustment model of ancillary-care obligations, in turn, has substantive implications for how to deal ethically with incidental findings; for instance, it suggests that researchers have no moral obligation to hunt for incidental findings.     

Protection of human subjects; informed consent--FDA. Final rule

The Food and Drug Administration (FDA) is amending its current informed consent regulations to permit harmonization of the Department of Health and Human Services' (DHHS) policies on emergency research and to reduce confusion on when such research can proceed without obtaining an individual subject's informed consent. This regulation provides a narrow exception to the requirement for obtaining and documenting informed consent from each human subject, or his or her legally authorized representative, prior to initiation of an experimental intervention. The exception would apply to a limited class of research activities involving human subjects who are in need of emergency medical intervention but who cannot give informed consent because of their life-threatening medical condition, and who do not have a legally authorized person to represent them. FDA is taking this action in response to growing concerns that current rules are making high quality acute care research activities difficult or impossible to carry out at a time when the need for such research is increasingly recognized.     

A METHODOLOGICAL ADDITION TO THE CROSS‐NATIONAL EMPIRICAL LITERATURE ON SOCIAL STRUCTURE AND HOMICIDE: A FIRST TEST OF THE POVERTY‐HOMICIDE THESIS*

Dozens of cross‐national studies of homicide have been published in the last three decades. Although nearly all these studies test for an association between inequality and homicide, no studies test for a poverty—homicide association. This absence is disconcerting given that poverty is one of the most consistent predictors of area homicide rates in the abundant empirical literature on social structure and homicide in the United States. Using a sample that coincides closely with similar recent studies, applying a proxy for poverty (infant mortality) that is commonly employed in noncriminological cross‐national research, and controlling for several common covariates (including inequality), this study provides the first test of the poverty—homicide hypothesis at the cross‐national level. The results reveal a positive and significant association between a nation's level of poverty and its homicide rate. The findings also suggest that we may need to reassess the strong conclusions about an inequality—homicide association drawn from prior studies, as this relationship disappears when poverty is included in the model.     

Managing incidental findings in human subjects research: analysis and recommendations.

No consensus yet exists on how to handle incidental findings (IFs) in human subjects research. Yet empirical studies document IFs in a wide range of research studies, where IFs are findings beyond the aims of the study that are of potential health or reproductive importance to the individual research participant. This paper reports recommendations of a two-year project group funded by NIH to study how to manage IFs in genetic and genomic research, as well as imaging research. We conclude that researchers have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB, and in their consent forms and communications with research participants. Researchers should establish a pathway for handling IFs and communicate that to the IRB and research participants. We recommend a pathway and categorize IFs into those that must be disclosed to research participants, those that may be disclosed, and those that should not be disclosed.     

Finding the Balance: Intoxication and Consent

Sexual offences in England and Wales have had a dramatic reimagining in the last 15 years, with the Sexual Offences Act 2003 establishing not only the boundaries of the most heinous of offences such as rape, but also defining one of the most important elements; consent. This article seeks to explore the problems that surround establishing if legally valid consent has been given, with particular regard for cases where voluntary intoxication takes centre stage. The problem that often arises is the question on whether or not an intoxicated victim had the capacity to consent, or establishing if she did consent when memory of the event is hazy, possibly from both parties. Using comparative analysis with other jurisdictions and their take on the offence of rape, the author seeks to discover if the current rules are sufficient to fit within twenty-first century western culture. The victim will be referred to as ‘she’, although the law here and all situations discussed are equally applicable to male rape.

     

Bridging philosophical and practical implications of incidental findings in brain research

Empirical studies and ethical-legal analyses have demonstrated that incidental findings in the brain, most commonly vascular in origin, must be addressed in the current era of imaging research. The challenges, however, are substantial. The discovery and management of incidental findings vary, at minimum, by institutional setting, professional background of investigators, and the inherent differences between research and clinical protocols. In the context of human subjects protections, the challenges of disclosure of unexpected and potentially meaningful clinical information concern privacy and confidentiality, communication, and responsibility for follow-up. Risks, including a blurring of boundaries between research and clinical practice, must be weighed against the possible benefit to subjects and a moral duty to inform. Identification and examination of these challenges have been met by scientific interest and a robust, interdisciplinary response resulting in the pragmatic recommendations discussed here.     

Incidental findings in human subjects research: what do investigators owe research participants?

The use of brain imaging technology as a common tool of research has spawned concern and debate over how investigators should respond to incidental findings discovered in the course of research. In this article, we argue that investigators have an obligation to respond to incidental findings in view of their entering into a professional relationship with research participants in which they are granted privileged access to private information with potential relevance to participants' health. We discuss the scope and limits of this professional obligation to respond to incidental findings, bearing in mind that the relationship between investigators and research participants differs fundamentally from the doctor-patient relationship.     

Social perception of rape victims

Since 1975, 40 states have enacted “rape shield” statustes which limit the admissibility of a rape victim's prior sexual history in court. These reforms have assumed that jurors regard prior sexual history evidence as much too probative of a victim's credibility and moral character, and that such perceptions have a prejudicial impact on the outcome of the jury decision process. The present research adopted an attributional analysis in order to examine the extent to which the types of legal reform affect social perception of the victim as well as the conviction rate in a videotaped consent defense rape trial. A large-scale jury simulation experiment was conducted with qualified jurors from the Minneapolis-St. Paul metropolitan area. Jurors either viewed an Improbable or Probable Likelihood of (victim) Consent version of the trial, with admission of prior sexual history evidence governed by one of three types of exclusionary rules. The results lend credence to the reformist contention that a rape victim is “on trial” along with the accused. Jurors were reluctant to convict when any testimony about prior sexual history was introduced. Moreover, jurors' close scrutiny of the victim's credibility and moral character was directly related to the conviction rate. Only the most restrictive evidentiary rule, when applied to an Improbable Consent case, curtailed the inference of victim consent, enhanced victim credibility, and increased the likelihood of conviction. Some of the legal and attributional implications of these findings were discussed.     

The Data Protection (Amendment) Act, 2003: the Data Protection Directive and its implications for medical research in Ireland

Directive 95/46/EC on the Protection of Individuals with regard to the Processing of Personal Data and on the Free Movement of Such Data has been transposed into national law and is now the Data Protection (Amendment) Act, 2003. The Directive and the transposing Act provide for new obligations to those processing data. The new obligation of primary concern is the necessity to obtain consent prior to the processing of data (Article 7, Directive 95/46/EC). This has caused much concern especially in relation to 'secondary data' or 'archived data'. There exist, what seem to be in the minds of the medical research community, two competing interests: (i) that of the need to obtain consent prior to processing data and (ii) the need to protect and foster medical research. At the same time as the introduction of the Act, other prior legislation, i.e. the Freedom of Information Act, 1997-2003, has encouraged candour within the doctor-patient relationship and the High Court in Ireland, in the case of Geoghegan v. Harris, has promulgated the 'reasonable-patient test' as being the correct law in relation to the disclosure of risks to patients. The court stated that doctors have a duty to disclose all material risks to patients. The case demonstrates an example of a move toward a more open medical relationship. An example of this rationale was also recently seen in the United Kingdom in the House of Lords decision in Chester v. Afshar. Within the medical research community in Ireland, the need to respect the autonomy of patients and research participants by providing information to such parties has also been observed (Sheikh A. A., 2000 and Irish Council for Bioethics, 2005). Disquiet has been expressed in Ireland and other jurisdictions by the medical research communities in relation to the exact working and meaning of the Directive and therefore the transposing Acts (Strobl et al). This may be due to the fact that, as observed by Beyleveld "The Directive makes no specific mention of medical research and, consequently, it contains no provisions for medical research as an explicitly delineated category." (Beyleveld D., 2004) This paper examines the Irish Act and discusses whether the concerns expressed are well-founded and if the Act is open to interpretation such that it would not hamper medical research and public health work.     

UNPACKING THE RELATIONSHIP BETWEEN ADOLESCENT EMPLOYMENT AND ANTISOCIAL BEHAVIOR: A MATCHED SAMPLES COMPARISON*

A large body of research has consistently found that intensive employment during the school year is associated with heightened antisocial behavior. These findings have been influential in prompting policy recommendations to establish stricter limits on the number of hours that students can work during the school year. We reexamine the linkage between first‐time work at age 16 during the school year and problem behaviors. Our analysis uses group‐based trajectory modeling to stratify youths based on their developmental history of crime and substance abuse. This stratification serves to control for preexisting differences between workers and nonworkers and permits us to examine whether the effect of work on problem behaviors depends on the developmental history of those behaviors. Contrary to most prior research we find no overall effect of working on either criminal behavior or substance abuse. However, we do find some indication that work may have a salutary effect on these behaviors for some individuals who had followed trajectories of heightened criminal activity or substance abuse prior to their working for the first time.     

Donation of 'spare' fresh or frozen embryos to research: who decides that an embryo is 'spare' and how can we enhance the quality and protect the validity of consent?

This paper analyses elements of the legal process of consent to the donation of 'spare' embryos to research, including stem-cell research, and makes a recommendation intended to enhance the quality of that process, including on occasion by guarding against the invalidity of such consent. This is important in its own right and also so as to maximise the reproductive treatment options of couples engaged in in vitro fertilisation (IVF) treatment and to avoid possible harms to them. In Part 1, with reference to qualitative data from three UK IVF clinics, we explore the often delicate and contingent nature of what comes to be, for legal purposes, a 'spare' embryo. The way in which an embryo becomes 'spare', with its implications for the process of consent to donation to research, is not addressed in the relevant reports relating to or codes of practice governing the donation of embryos to research, which assume an unproblematic notion of the 'spare' embryo. Significantly, our analysis demonstrates that there is an important and previously unrecognised first stage in the donation of a 'spare' embryo to research, namely: consent to an embryo being 'spare' and so, at the same time, to its disuse in treatment. This is not explicitly covered by the Human Fertilisation and Embryology (HFE) Act 1990, as amended by the HFE Act 2008. Having identified this important initial stage in the process of consent to the donation of a 'spare' embryo to research in conclusion to Part 1, in Part 2 we analyse the idea of consent to an embryo's disuse in treatment on the basis that it is 'spare' with reference to the legal elements of consent, namely information as to nature and purpose, capacity, and voluntariness. We argue that there are in fact three related consent processes in play, of which the principal one concerns consent to an embryo's disuse in treatment. If the quality of this first consent is compromised, in turn this will impact on the quality of the consent to the donation of that 'spare' embryo to research, followed by the quality of consent to future cycles of assisted reproduction treatment in the event that these are needed as a result of a donation decision. The analysis overall is of central relevance to the debate as to whether, and if so when, it should be permissible to request the donation of fresh embryos for research, as opposed to those that have been frozen and, for instance, have reached the end of their statutory storage term. This has a particular bearing on the donation of embryos to stem-cell research since there is a debate as to whether fresh embryos are most useful for this.     

Undermining Prima Facie Consent in the Criminal Law

Even when a person appears to have consented to another’s interference with her interests, we sometimes treat this apparent consent as ineffective. This may either be because the law does not permit consent to validate the actions concerned, or because the consent is undermined by the presence of additional factors which render it insufficiently autonomous to be effective. In this paper I propose that the project of categorising and systematically analysing the latter set of cases, would be furthered by recognising (1) that prima facie consent is undermined when the prima facie consenter’s autonomy to choose whether or not to consent has been unfairly constrained, and (2) that theoretical and doctrinal clarity can be promoted by analysing the factors that unfairly constrain autonomy in the criminal law using a framework developed in contract law to determine analogous questions arising in relation to assent to a contract.     

The Future of Incidental Findings: Should They be Viewed as Benefits?

This paper argues against considering incidental fndings (IFs) as potential benefts of research when assessing the social value of proposed research, determining the appropriateness of a study's risk/beneft ratio, and identifying and disclosing the risks and benefts of participation during informed consent. The possibility of generating IFs should be disclosed during informed consent as neither a risk nor beneft, but as a possible outcome collateral to participation. Whether specifc IFs will be disclosed when identifed is a separate question whose answer is material to determining whether IFs constitute a risk or a potential indirect beneft of participation. Finally, three types of IF should be distinguished and treated diferently during informed consent: those that will be routinely generated (e.g., results of testing to determine study eligibility), those that can reasonably be characterized in terms of their nature and frequency of generation (e.g., misattributed parentage), and those of unpredictable nature and frequency that can be characterized only in general terms. Research protocols should provide a rationale for sharing or not sharing IFs of these three types with participants. Regulatory review of such plans should not, however, be confused with regarding IFs as potential benefts when assessing the study's risk/beneft ratio or merit.