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Background: It is unclear how the possible effects of genetic research on socially identifiable groups may impact patient willingness to donate biological samples for future genetic studies., Methods: Telephone interviews with patients at 5 academic medical centers in the U.S. examined how patients' beliefs about benefits and harms to ones racial or ethnic group shape decisions to participate in genetic research., Results: Of the 1,113 patients who responded to questions about group harms and benefits, 61% of respondents indicated that potential benefits to their own racial or ethnic group would be a big or moderate part of their decision to donate a sample for genetic research. 63% of black respondents and 57% of white respondents indicated that they were 'very' or 'moderately concerned' about genetic research findings being used to discriminate against people by race or ethnicity. 64% of black and 34% of white respondents reported that their willingness to donate a blood sample would be substantially reduced due to these concerns., Conclusion: Our findings suggest that a key factor in many patients' decisions to donate samples for genetic research is how those studies may impact identifiable racial and ethnic groups. Given the importance of these considerations to many patients, our study highlights a need to address patients' concerns about potential group benefits and harms in the design of future research studies and DNA biobanks., (Copyright © 2010 S. Karger AG, Basel.)

Objective: To assess how Institutional Review Boards (IRBs) implement the assent requirement for research with children., Methods: Telephone interviews were conducted with 188 chairpersons of IRBs from a range of institutions nationwide. Respondents were queried on 4 topics: 1) which children are considered capable of assent, 2) which information investigators must provide pediatric research subjects, 3) whether IRBs favor the enrollment of children who are capable of assent, and 4) how chairpersons view payment for children's research participation., Results: Half of IRBs have a method that they require investigators to follow when determining which children are capable of assent, most commonly an age cutoff. Half of IRBs do not have a method, and the majority rely on investigators' clinical judgment. IRBs largely follow the adult research regulations when determining which information should be provided to an assenting child. A total of 58% of IRBs would enroll a child who is incapable of assent in a nonbeneficial study, even if children who are capable of assent could be enrolled instead. Almost half (46%) of chairpersons believe that it sometimes or always acceptable to offer incentive payments to children, and more than one third (35%) thought it acceptable to offer payment to the parents., Conclusion: When possible, IRBs follow the federal regulations for research with adults when implementing the assent requirement. For considerations that do not have analogs in the adult regulations, IRB practices vary widely. These data suggest that IRBs need guidance on how to implement the assent requirement in a way that provides appropriate protections for pediatric research subjects.

Context: Federal regulations allow children in the United States to be enrolled in clinical research only when the institutional review board (IRB) determines that the risks are minimal or a minor increase over minimal, or that the research offers a prospect of direct benefit. Despite this reliance on IRBs, no data exist on how IRBs apply the risk and benefit categories for pediatric research., Objective: To determine how IRB chairpersons apply the federal risk and benefit categories for pediatric research., Design, Setting, and Participants: Telephone survey, conducted between May and August 2002 of 188 randomly selected chairpersons of IRBs in the Unites States. The survey consisted of 21 questions to assess the application of federal risk standards to research procedures, whether certain interventions offer a prospect of direct benefit to participating children, and the extent to which IRBs use the federal definition of minimal risk when categorizing the risks of research procedures in children., Main Outcome Measures: Responses regarding categorization of the risk level and direct benefits of pediatric research procedures., Results: A single blood draw was the only procedure categorized as minimal risk by a majority (152 or 81%) of the 188 respondents. An electromyogram was categorized as minimal or a minor increase over minimal risk by 100 (53%) and as more than a minor increase over minimal risk by 77 (41%). Allergy skin testing was categorized as minimal risk by 43 IRB chairpersons (23%), a minor increase over minimal risk by 81 (43%), and more than a minor increase over minimal risk by 51 (27%). Regarding benefits, 113 chairpersons (60%) considered added psychological counseling to be a direct benefit, while participant payment was considered a direct benefit by 10% (n = 19)., Conclusions: Application of the federal risk and benefit categories for pediatric research by IRB chairpersons is variable and sometimes contradicted by the available data on risks and the regulations themselves. To protect children from excessive risks while allowing appropriate research, IRB chairpersons need guidance on applying the federal risk and benefit categories and also need data on the risks children face in daily life and during routine physical or psychological tests.

Background: The inclusion of children with asthma in clinical asthma trials is increasing, including their participation in placebo-controlled trials (PCTs). The objectives of this study are to assess whether children with asthma have been harmed by their participation in PCTs., Methods: Seventy clinical asthma trials involving children published between January 1998 and December 2001 that involved distinct US research populations were identified. Studies were reviewed to determine whether all subjects with more than mild asthma received daily antiinflammatory medication as recommended by national guidelines. Sixty-two clinical asthma trials included data about subject withdrawal and were analyzed for the frequency of asthma exacerbations., Results: Forty-five studies were designed as PCTs and did not require that all subjects with more than mild asthma receive antiinflammatory medications. Of 24,953 subjects, 4653 (19%) for whom data are available withdrew from research, and 1247 subjects (9.4%) withdrew from PCTs due to asthma exacerbations compared with 358 subjects (3.1%) in other trials. In PCTs, subjects withdrew more frequently from the placebo arms than the active-treatment arms and did so more frequently because of an asthma exacerbation (667 or 15% vs 580 or 6.5%). Fifty-two studies enrolled both children and adults, although only 1 performed subset analysis of the children., Conclusions: Subjects enrolled in PCTs of asthma have been exposed to unnecessary risks and harms. Clinical asthma trials involving children and adults do not benefit children as a class because they rarely provide subset analysis of children subjects.

Background: Ethicists have suggested that written consent forms encourage participants in phase 1 cancer trials to expect benefit from the experimental agent and to overlook serious risks., Methods: To evaluate the written description of direct benefit as well as risk, all consent forms for 1999 phase 1 cancer trials were compiled from 80 percent of the National Cancer Institute-designated cancer centers and from six of eight large pharmaceutical developers of anticancer drugs. In each case, we evaluated the characteristics of the trial, the descriptions of the purpose and procedures of the research, the promise of benefit, the description of risks, and the description of alternatives., Results: Of 272 forms, 268 explicitly mentioned that the trial was research, and 249 stated that the purpose of the trial was testing for safety. Nearly all forms (269) mentioned the right to withdraw from the trial. Almost all forms (260) referred to the experimental agent as "treatment" or "therapy." Only one consent form promised direct benefit to subjects. Most forms (181) mentioned death as a risk, and very few (14) mentioned cure as even a possible benefit. Most (229) stated that there was unknown risk involved and indicated that severe or permanent harms were possible (224)., Conclusions: Consent forms for phase 1 oncology studies almost never promise direct benefit to subjects, rarely mention cure, and usually communicate the seriousness and unpredictability of risk. Although there is room for improvement, the substance of these forms is unlikely to be the primary source of misunderstanding by subjects in phase 1 oncology trials., (Copyright 2002 Massachusetts Medical Society)

Newborn screening for cystic fibrosis (CF) remains controversial largely because its implementation is less a scientific decision than a resolution of different and often conflicting normative values that underlie the policy issues framing the debate. This article summarizes the literature published between May 2001 and April 2002 (and relevant earlier literature) regarding the screening and treatment goals, clinical benefits and harms, and programmatic and ethical issues. Finally, we will present an analysis to argue for one set of ethical considerations that point to very specific policy recommendations that would justify CF newborn screening in certain circumstances and make its implementation more ethically appropriate.

Only 10 years after the first human gene transfer protocols were approved for adults and children, researchers have begun to consider gene transfer on the fetus. While preliminary animal research is ongoing, the enthusiasm and pace of research in this area suggest that human protocols for in utero gene transfer research may be seriously considered in the foreseeable future. Federal guidelines for fetal research rely on minimizing risk and informed consent to protect the "rights and welfare" of both the fetus and pregnant woman. However, in utero gene transfer research poses special challenges to informed consent. This research represents an innovative approach for very ill subjects and takes place in the prenatal setting. These features may converge to undermine the expectant parents' comprehension of, and voluntariness for participation in, research. In this case, informed consent may not be able to bear the weight of adequately protecting the fetus from undue research risks. To compensate for this limitation, and using the regulations for pediatric research as a guide, a greater emphasis should be placed on the benefit/harm assessment rather than informed consent. Selecting diseases/patients where good alternative treatments exist may maximize informed consent, yet this may be a trade-off that exposes the fetus to greater relative risks. On the other hand, selecting diseases/patients without good alternative treatments to prolong life may convey an overestimation of the potential benefits of these interventions, and although care should be taken to strive to improve understanding of these limitations, misunderstanding may persist. However, selecting diseases/patients with no good alternatives might make serious risks more tolerable, and this should take precedence over informed consent. The limitations of informed consent brought into focus by the special features of in utero gene transfer research may be relevant to a broader range of innovative investigations.

Authors examine the ethical and health policy implications in the Cancer Genetic Studies Consortium projects, which attempt to collect data on the clinical benefits and harms of cancer genetic testing. They suggest that more data are needed on the long-term physical and psychosocial effects of testing and that further examination is needed of the ethical issues raised by testing.

In recognition of the earlier experiences with genetic diagnostic services and in anticipation of a greater potential for genetic testing for presymptomatic disease and disease susceptibility, this article provides an analysis of policy development for cystic fibrosis carrier screening. The deficiencies of relying on an extemporaneous model for health policy development are described. Preferably, an evidentiary model, based on the evaluation of clinical research and incorporating professional and public attention to underlying normative issues, should define the standard of care. Appropriate procedural mechanisms should be established at both state and federal levels to prevent the unnecessary confusion, expense, and personal or social harms likely to result from a completely unrestrained application of developing genetic technologies or continuing ad hoc responses to rapid increases in genetic diagnostic capabilities. A broadly constituted national advisory commission on the ethical, legal, and social implications of the Human Genome Project would provide an important locus for national decision making and may offer an efficient mechanism for implementing the evidentiary model, promoting public involvement at a time when social policy decisions must be made to restructure the health care system to be more sensitive to issues of access, allocation, and costs.

Many questions remain regarding the efficacy, toxicity, and costs of CF neonatal screening. It would be premature, in our opinion, to implement mass population screening of newborns for CF until the benefits and risks have been fully defined, and an adequate and logistically feasible testing system developed and/or highly effective therapy for CF lung disease becomes available. In addition, the ethical issues described herein need to be resolved. This pertains not only to the CF patient but also the heterozygote carrier. These reservations notwithstanding, the discovery of the CF gene should have a favorable impact both directly and indirectly on neonatal screening for the disease. Mutation analysis coupled to IRT testing seems most attractive at this time, at least on a research basis, but primary molecular diagnostic procedures might supervene in the future, particularly if they are financially feasible.