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.     

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.     

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.     

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 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.     

The current state of medical school education in bioethics, health law, and health economics.

Current challenges in medical practice, research, and administration demand physicians who are familiar with bioethics, health law, and health economics. Curriculum directors at American Association of Medical Colleges-affiliated medical schools were sent confidential surveys requesting the number of required hours of the above subjects and the years in which they were taught, as well as instructor names. The number of relevant publications since 1990 for each named instructor was assessed by a PubMed search. In sum, teaching in all three subjects combined comprises less than two percent of the total hours in the American medical curriculum, and most instructors have not recently published articles in the fields they teach. This suggests that medical schools should reevaluate their curricula and instructors in bioethics, health law, and health economics.     

To bite or not to bite: Canine apprehensions in a large, suburban police department

There is a dearth of empirical research on the use of police canines. This article examines the use of canines in a large, suburban police department over a six-year period (1993-1998). Use of force reports, canine-apprehension reports, arrest data, and the canine unit's monthly activity reports were reviewed. Five rates were calculated: (1) canine-apprehension rate, (2) canine bite rate, (3) rate of bites resulting in any medical treatment, (4) rate of bites resulting in medical treatment at a hospital, and (5) officer injury rate. Of the suspects apprehended by canines, 14.1 percent were bitten, 9.1 percent received medical attention (on the scene or at a hospital), and 4.8 percent received medical attention at a hospital. The canine bite rate was significantly lower for non-White suspects than for White suspects. The use of rate-based information for the evaluation of policy and procedure concerning the use of police canines is discussed.     

Treatment of research-related injuries to human subjects--VA. Final rule

This final rule amends the Department of Veterans Affairs (VA) medical regulations to provide (or to pay for the provision of) necessary medical treatment to certain human subjects injured as a result of participation in VA research. Under the final rule all participants in research approved by a VA Research and Development Committee (regardless of source of funding), and conducted under the supervision of one or more VA employees, are eligible for treatment unless injuries are due to noncompliance by a research subject with study procedures. VA will provide medical care in those circumstances where VA has some responsibility for the need for medical care.     

Participation of children in clinical trials: UK, European and international legal perspectives on consent

The Declaration of Helsinki was, until recently, the leading international code on the conduct of clinical trials on human subjects. The Council of Europe's Convention on Human Rights and Biomedicine (1997) and the ICH guidelines for Good Clinical Practice (1996) represent a significant step towards increased harmonization of standards in the conduct of medical experiments on human subjects. But in spite of emerging areas of consensus, there remain important areas of unclarity and divergence. Medical practitioners involved in paediatric research in the UK are concerned about the lack of certainty in the law, particularly on the application of consent rules to emergency research. This paper examines UK, European and International norms on the participation of children in medical research and compares the circumstances under which consent rules may be waived under each normative regime.     

活体鉴定400例放射学特点分析──兼论法医临床学与放射学的关系

为探讨法医临床学鉴定与放射学的关系，本文对４００例活体鉴定就放射学检查的有关问题进行回顾性研究。结果表明：２６６例进行了放射学检查（占６６．５％），其中Ｘ线１７６例（６６．２％），ＣＴ４３例（１６．１％），两者均有的４７例（１７．７％）。放射学检查部位中，Ｘ线以四肢为多，ＣＴ以颅脑为多。误诊率为９．０２％，放射学检查与致伤原因之间有一定关系，轻微伤中不必要的ＣＴ检查多见。并就放射学误诊的法律后果及不必要的放射学检查问题进行了讨论。本文从法医临床学的角度对放射学进行了评价，指出在活体鉴定中可以应用放射学知识协助证明损伤、推断损伤形成机制、个人识别及研究损伤时间。因此法医学鉴定人必须有放射学理论和技术方面的知识。作者还试图提出法医临床放射学。     

A comparison between the Intercept Oral Fluid Collection Device® and urinalysis among Baltimore City probationers

Few studies compared oral fluid (OF) analysis to laboratory urinalysis (UA) in real-world criminal justice environments, and no studies had collected survey data, from either specimen providers or specimen collectors, about the overall OF collection experience. In the most comprehensive toxicological comparison study conducted to date, urine and OF specimens were collected from a sample of 223 adult probationers in Baltimore City, Maryland, between March and May 2004. In addition, probationers and probation staff were surveyed about the OF collection experience. With confirmed UA as the reference standard, the Intercept Oral Specimen Collection Device® (Intercept) was 100 percent sensitive and 99 percent specific for benzodiazepines, 92 percent sensitive and 96 percent specific for cocaine, 77 percent sensitive and 96 percent specific for opiates, 39 percent sensitive and 98 percent specific for marijuana, and 75 percent sensitive and 91 percent specific for the detection of at least one drug. Seventy-two percent of the probationers and 88 percent of the probation staff rated the Intercept experience better than the collection of urine specimens. Implications for criminal justice policy and research are discussed.     

Medical Evidence and Expert Testimony in Child Sexual Abuse

Expert medical testimony in child sexual abuse cases can be critical to the outcome of a legal case. This article will review the development of the medical knowledge and clinical expertise in child sexual abuse. Since the passage of mandatory child abuse reporting laws, the forensic medical examination of a child for evidence of sexual abuse has become standard. Until recently, many myths regarding female genital anatomy existed but were based primarily on dogma and lack of empirical research. Over the past 25 years, many research studies and accumulating clinical evidence have expanded medical knowledge and debunked old myths. Physical evidence, even in cases of alleged genital or anal penetration is rare. Sexually transmitted infections are also uncommon and often require medical interpretation as to their significance in a prepubertal child. Specialized medical knowledge, training, and clinical expertise have developed in order to evaluate children presenting with allegations of sexual abuse. Such medical expertise provides invaluable service to courts. We review criteria for evaluating such expertise in light of current medical practice.     

PULLING BACK THE CURTAIN ON HERITABILITY STUDIES: BIOSOCIAL CRIMINOLOGY IN THE POSTGENOMIC ERA

Unfortunately, the nature‐versus‐nurture debate continues in criminology. Over the past 5 years, the number of heritability studies in criminology has surged. These studies invariably report sizeable heritability estimates (～50 percent) and minimal effects of the so‐called shared environment for crime and related outcomes. Reports of such high heritabilities for such complex social behaviors are surprising, and findings indicating negligible shared environmental influences (usually interpreted to include parenting and community factors) seem implausible given extensive criminological research demonstrating their significance. Importantly, however, the models on which these estimates are based have fatal flaws for complex social behaviors such as crime. Moreover, the goal of heritability studies—partitioning the effects of nature and nurture—is misguided given the bidirectional, interactional relationship among genes, cells, organisms, and environments. This study provides a critique of heritability study methods and assumptions to illuminate the dubious foundations of heritability estimates and questions the rationale and utility of partitioning genetic and environmental effects. After critiquing the major models, we call for an end to heritability studies. We then present what we perceive to be a more useful biosocial research agenda that is consonant with and informed by recent advances in our understanding of gene function and developmental plasticity.     

Transforming Prevention Systems in the United States and The Netherlands Using Communities That Care

Josine Junger-Tas introduced the Communities That Care (CTC) prevention system to the Netherlands as a promising approach to address the growing youth violence and delinquency. Using data from a randomized trial of CTC in the United States and a quasi-experimental study of CTC in the Netherlands, this article describes the results of a comparison of the implementation of CTC in 12 U.S. communities and five Dutch neighborhoods. CTC communities in both countries achieved higher stages of a science-based approach to prevention than control communities, but full implementation of CTC in the Netherlands was hampered by the very small list of prevention programs tested and found effective in the Dutch context.     

Medical criminalistics

Medical criminalistics is an essential part of legal/forensic medicine. It includes the clinical examination of surviving victims and suspects, the inspection of the scene in suspicious deaths with subsequent performance of medico-legal autopsies, the assessment of (biological) traces and the reconstruction of criminal events under medical aspects. Just as the circumstances of life and the manifestations of crime are changing with time, there is a permanent alteration regarding the issues of medical criminalistics. Legal/forensic medicine is a university subject in most countries and therefore, research work is one of the main tasks also in medical criminalistics. In contrast to clinical medicine and basic research, some common study designs are not suitable for the special needs of medical criminalistics, whereas other types are more appropriate like epidemiological evaluations, cross-sectional studies and (retrospective) observation studies. Moreover, experimental model tests and case reports also rate high in medical criminalistics.     

Neurovisualization methods in diagnostics of consequences in light craniocerebral trauma

The purpose of the case study was to elucidate the frequency rate of pathological changes as registered by computer tomography (CT) and magnetic-resonance tomography (MRT) of the head in patients with chronic cerebral blood-circulation deficiency (CBD), functional disorders and vegetative nervous pathologies in presence (in their medical histories) of closed-type cranial trauma concomitant with concussion of the brain (CB) or without such trauma. A comparative analysis revealed a minor prevalence in the number of pathological changes in patients with CBD concomitant with CB. As for other nosological forms, the quantities of changes, expressed in percent, were virtually identical. A conclusion was made on the need to examine the patients of the discussed category by neurovisualization in the acute and remote periods of trauma.     

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.     

Diagnostic x-ray systems and their major components; amendments to performance standard--FDA. Final rule

The Food and Drug Administration (FDA) is amending the performance standard for diagnostic x-ray systems and their major components by revising and adding requirements concerning computed tomography x-ray (CT) systems. CT systems are new medical diagnostic tools whose use in the United States has grown significantly in recent years. Because CT systems have many performance features that are unlike conventional x-ray systems, the current performance standard for diagnostic x-ray systems is not entirely appropriate for CT systems. The amendments to the standard address the special characteristics of CT systems.     

Status and prospects in developing morphologic studies in forensic medicine

Modern state of forensic medical morphological studies is analyzed. Main trends of research are reviewed (personality identification, diagnosis of acute alcohol and narcotic poisoning, morphology of craniocerebral injury, development of criteria for identifying the time when injuries were inflicted). Shortcomings in these studies and in practical forensic medical histological service are discussed. Prospects for further studies are outlined.