Institutional review board approaches to the incidental findings problem

Institutional Review Boards (IRBs) are confronted with new challenges in the face of expanding technologies while fulfilling their existing regulatory mandate to ensure that plans are in place to protect subjects and to inform them of risks and benefits of research participation. Existing regulations and guidance do not address the issue of incidental findings (IFs), thus leaving awareness of the issue and the application of ethical principles to IRB judgment alone. In order to assure that researchers are aware of the potential for IFs, IRBs must identify which studies are likely to identify IFs and establish what plans should be put into place prior to study initiation to assure the subjects are appropriately informed of the likelihood of IFs, how IFs will be communicated to subjects, and whether the burden of follow-up falls on the researchers or is the subject's responsibility.     

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.     

Legal liability and research ethics boards: the case of neuroimaging and incidental findings

Neuroimaging research covers a wide range of intriguing issues from revealing brain structures to investigating what happens in our brain when we lie. The field appears to be thriving, but skepticism and alertness to the various ethical, scientific, policy and philosophical challenges associated with it also appear to be on the rise. One particularly complex issue concerns what to do with incidental findings that emerge during the course of neuroimaging research. Research ethics boards (REBs) play a central role in research oversight. In this paper, we will consider some of the potential issues associated with REB liability in negligence in the context of incidental findings in neuroimaging research.     

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.     

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.     

The risks and benefits of searching for incidental findings in MRI research scans.

We weigh the presumed benefits of routinely searching all research scans for incidental findings (IFs) against its substantial risks, including false-positive and false-negative findings, and the possibility of triggering unnecessary, costly evaluations and perhaps harmful treatments. We argue that routinely searching for IFs may not maximize benefits and minimize risks to participants.     

The ethics of promulgating principles of research ethics: the problem of diversion effects

There is an important distinction between ethical standards for the conduct of research with human subjects and the ethics of promulgating principles of research ethics. Those who promulgate ethical standards for the conduct of research have an ethical responsibility to consider the consequences to which those promulgations give rise. In particular, they must consider whether their promulgations will give researchers incentives not to conduct research or not to conduct research in locales in which participants would benefit from participation. I first show how such ‘diversion effects’ are possible and then examine four principles of research ethics in that light. I then consider several objections to the argument that those who promulgate principles of research ethics should consider diversion effects.     

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.     

Incidental findings and future testing methodologies: potential application of the ACMG 2013 recommendations

Reactions to the first clinical recommendations for the return of incidental findings (IFs) from genomic sequencing published by the American College of Medical Genetics and Genomics (ACMG) were polarized and resolute. Exploring the three main points of controversy: mandatory testing, testing children for adult conditions, and selection of conditions to be reported on, illuminates concerns for and conservation of bioethical principles—specifically, autonomy and non-directiveness. With the historical context of genetic testing in mind, this article studies the potential application of the ACMG recommendations to embryonic testing in the form of preimplantation genetic diagnosis. Theoretical extension of the current recommendations assists in the identification of bioethical dilemmas and possible societal impacts. The recommendations make a statement on the importance of diagnosis and intervention for specific genetic conditions, setting a precedent for disease classification and patient autonomy. In the extreme, the clinical application of such recommendations prenatally may result in discarded embryos, and less societal tolerance of specific conditions. Skilled professionals, such as genetic counselors, researchers, and lawmakers must work together to maintain patient autonomy, providing care in the best interest of each patient.     

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.     

Incidental findings in magnetic resonance imaging (MRI) brain research

The use of magnetic resonance imaging (MRI) to investigate brain structure ("structural MRI") and function (so-called "functional MRI") has become increasingly common among neuroscientists, psychologists, and even economists in recent years. Yet, despite this increase in use, relatively little attention has been paid to the issue of incidental findings. The current paper discusses these issues, and anticipates the future of incidental findings in the context of other neuroimaging tools currently being used to investigate the living brain.     

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?     

论规范性文件不予一并审查:判断要素及其认定规则——基于1799份裁判文书的分析

规范性文件“能否一并审查”是对规范性文件合法性进行实质审查的先决问题。根据现有的制度规定,可将司法实践中规范性文件不予一并审查的类型划分为基础性要件缺失、附带性要件缺失和例外情形等三类,每种类型都包含多种情形和不同判断要素。法院应当采取更加积极宽容的态度,尽可能地将更多的规范性文件纳入一并审查的范围。对于不予一并审查的规范性文件的认定,应当在区分规范性文件与非规范性文件的基础上,综合运用多种认定标准明确界定规范性文件排除审查的范围。应当赋予第三人一并审查的请求主体资格,并明确当事人延迟提出一并审查请求“正当理由”的判断标准。对于不予一并审查例外情形的认定,应审慎对待,严格约束法院司法裁量权的行使。     

Incidental findings in genetics research using archived DNA

Despite calls by some commentators for disclosing incidental findings in genetics research, several factors weigh in favor of caution. The technology of genetics has the power to uncover a vast array of information. The most potent argument for restraint in disclosure is that much research is pursued without consent so that the individual participant may not know that research is being conducted at all. Often the work is done by investigators and at institutions with which the person has no prior contact. Past practice is also relevant; genetics researchers historically have chosen not to disclose incidental findings, of which misattributed paternity and pleiotropic alleles such as ApoE have been the most common. Many people choose not to have genetic tests when given a choice. It may be desirable to discuss the topic of incidental findings when consent for research is obtained, but given the risk of unwanted surprise when there has been no prior discussion, the potential utility of incidental findings should be very high before they are even offered to individuals.     

Are ethics promulgations self-defeating?

Alan Wertheimer argues that promulgating some ethical standards of international clinical research may be self-defeating: the intended purpose of these standards is to promote the interests of subjects and communities in LMICs, while the outcome of promulgation could be to undermine these very same interests. If enforced, such standards would increase the costs of performing beneficial research in LMICs, potentially diverting opportunities to participate in this research away from those who have no other access to the care participation allows. I argue that these standards are really intended as deontological constraints protecting subjects from being exploited by research sponsors. First, I show that Wertheimer begs the question against this deontological interpretation of ethics promulgations, rejecting it on non-deontological grounds. I go on to show that non-exploitation is an important goal on its own, sometimes independent from—and sometimes even outweighing—the goal of promoting the interests of subjects and communities in LMICs. I conclude by suggesting that those who criticize the promulgation of non-exploitation on the grounds that exploitative practices help those badly off might do best to reconsider the background assumption that sponsors in wealthier countries have no pre-existing obligation to promote the interests of the world''s poor.     

Genomic research and incidental findings.

The Human Genome Project showed that there is significant genetic variation within the population. Current research is accumulating large databases that may reveal genetic variations associated with disease or health risks, even if not intended as part of the study design. These incidental findings create legal, ethical, and financial challenges for researchers. Current federal and international guidelines are not adequate. Plans for dealing with incidental findings need to be established in the study design and reviewed and approved by the Institutional Review Board.     

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.     

Attitudes of police officers toward their professional ethics

Professions are guided by codes of ethics to aid them in performance of their duties and to ensure maintenance of high standards of conduct. Police officers are faced with a maze of obligations in the performance of their official duties. The “Law Enforcement Code of Ethics” and “Canons of Police Ethics” were created to make explicit the conduct considered appropriate for police officers and to guide them in the performance of their duties.This study investigates how police officers in several police agencies view their professional ethics. Some of the broader questions examined in the study are the following: Do police officers have a clear understanding of the “Law Enforcement Code of Ethics” and the “Canons of Police Ethics?” Do they feel constrained by agency, societal, or other factors from behaving professionally? Do they consider their ethics adequate to guide professional conduct, and are they willing to abide by the principles? The responses indicate reliance on personal ethics in situations where standard police ethics are not clear, and suggest the need for further research in police ethics.     

手术并发症发生因素与医疗过错鉴定

医疗损害案件中因手术并发症而导致的占了很大的比重。发生手术并发症的发生原因可归结为医疗与患者两个方面。医疗方面的因素主要包括手术人员的责任心不强、医学基础知识欠缺、医疗技术生疏、诊断失误、术后护理及管理缺陷等;患者方面的因素主要有自身解剖变异、个体体质差异等。手术并发症产生的原因大多是可以被认知的,在此基础上判断产生手术并发症的医疗行为是否有过错时不能一概而论,应遵循一定的标准。建议按照医学理论和实际操作能力划分为两个标准,预见义务采用＂医学水平＂标准;防范义务采用＂医疗水平＂标准。通过两个＂标准＂来综合考量手术并发症才是科学的。     

Incidental findings in CT colonography: literature review and survey of current research practice

Incidental findings (IFs) of potential medical significance are seen in approximately 5-8 percent of asymptomatic subjects and 16 percent of symptomatic subjects participating in large computed tomography (CT) colonography (CTC) studies, with the incidence varying further by CT acquisition technique. While most CTC research programs have a well-defined plan to detect and disclose IFs, such plans are largely communicated only verbally. Written consent documents should also inform subjects of how IFs of potential medical significance will be detected and reported in CTC research studies.