Objective: To provide guidance on informed consent to clinicians offering cancer susceptibility testing.
Participants: The Task Force on Informed Consent is part of the Cancer Genetics Studies Consortium (CGSC), whose members were recipients of National Institutes of Health grants to assess the implications of cancer susceptibility testing. The 10 task force members represent a range of relevant backgrounds, including various medical specialties, social science, genetic counseling, and consumer advocacy.
Evidence.The CGSC held 3 public meetings from 1994 to 1996. At its first meeting, the task force jointly established a list of topics. The cochairs (G.G. and J.R.B) then developed an outline and assigned each topic to an appropriate writer and reviewer. Writers summarized the literature on their topics and drafted recommendations, which were then revised by the reviewers. The cochairs compiled and edited the entire manuscript. All members were involved in writing this report.
Consensus Process.The first draft was distributed to task force members, after which a meeting was held to discuss its content and organization. Consensus was reached by voting. A subsequent draft was presented to the entire CGSC at its third meeting, and comments were incorporated.
Conclusions: The task force recommends that informed consent for cancer susceptibility testing be an ongoing process of education and counseling in which (1) providers elicit participant, family, and community values and disclose their own, (2) decision making is shared, (3) the style of information disclosure is individualized, and (4) specific content areas are discussed.
EVOLUTION OF CANCER SUSCEPTIBILITY TESTING
Hereditary and acquired genetic mutations play a fundamental role in the development of cancer. [1] While most cancers result from acquired genetic alterations in somatic cells, some cancer patients have inherited mutations that play an etiologic role in their disease. More than 50 different types of cancer demonstrate a familial clustering suggestive of an inherited predisposition, including tumors of the breast, ovary, colon, and prostate. [2-8]
Genetic and epidemiologic research in families with an increased incidence of cancer has been useful for identifying risk-conferring mutations that are present in germline cells. The ultimate purpose of such research is to identify effective interventions for cancer prevention and treatment, and the pace of current discovery offers great promise in this respect. Unfortunately, at the present time, predictive genetic testing for many cancer-predisposing mutations, although technically possible, has limited utility for prevention or early detection of disease. [9,10] This gap between our ability to test for cancer susceptibility and our uncertain or limited ability to reduce mortality or morbidity contributes to psychosocial, ethical, and policy complexities. [11-14] These complexities make the process of educating potential test consumers about testing particularly important and problematic. As research about cancer-predisposing mutations progresses and test results are provided to consumers, the informed consent process must reflect these complexities.
Despite current recommendations by a number of professional societies that genetic testing for cancer susceptibility be confined to research protocols, [15,16] such testing is being introduced into clinical practice. [17] Since informed consent is as important in the clinical setting as it is in research, particular care must be taken by clinicians who do not have the benefit of institutional review board evaluations of their testing protocols. In 1994, the National Institutes of Health funded a group of studies to assess the ethical and psychosocial implications of testing for cancer-predisposing mutations. These and a small number of related projects formed the Cancer Genetics Studies Consortium (CGSC), which established a task force to explore the issue of informed consent for cancer susceptibility testing in both clinical and research settings. This statement is the result of the work of that task force.
WHY INFORMED CONSENT FOR GENETIC TESTING REQUIRES SPECIAL CONSIDERATION
One of the issues the task force discussed was whether such testing is sufficiently different from other types of medical tests to require special consideration for informed consent. There is no doubt that genetic information is similar in many respects to other kinds of medical information and that we can learn from our past experience with similar circumstances (eg, involving the human immunodeficiency virus [18]). The position we have taken is that even if genetic information is not unique, the challenges genetic testing presents to informed consent are sufficiently numerous to warrant special attention. Genetic information possesses all of the following characteristics at the same time: (1) it affects an entire family, rather than just a single individual [19]; (2) it is laden with symbolic meaning in our culture, partly because of the tendency to consider genes as uniquely deterministic of future health and behavior [20]; and (3) it presents unique challenges for medical professionals because of its probabilistic nature [21,22] and its implications for the reclassification of "patients" from healthy to at-risk. Specific to information about inherited susceptibility to cancer, the level of prediction is not certain, [23] yet no independent test is available to separate true from false positives, and the primary risks and benefits of testing at this time are psychological and social rather than physical (because the efficacy of preventive and therapeutic strategies has not been proven). The simultaneous presence of these characteristics makes genetic information more complex than other kinds of medical information.
The purpose of this article is to provide recommendations regarding informed consent for genetic testing for susceptibility to adult-onset cancers. This discussion is relevant to any testing context in which results are provided to patient-participants (hereafter referred to as participants). Most of our examples will refer to predictive testing for breast and ovarian cancers, but our recommendations are relevant to other forms of adult-onset cancer. This article will focus only on the testing of adults because predictive testing in children involves additional layers of complexity. [24] After providing a general background on informed consent, we will make specific recommendations for the process and content of consent for cancer susceptibility testing, as well as recommendations for future research on informed consent in this context.
BACKGROUND ON INFORMED CONSENT
General Theory of Informed Consent
The idea of informed consent has its origins in law, ethics, and our contemporary understanding in medicine about the nature of the physician-patient relationship. [21] The core notion is that any decisions about care involving a competent person are to be made in a collaborative manner between patient and physician and that the patient's authorization for a diagnostic procedure or treatment option be "intentional, substantially noncontrolled, and based on substantial understanding." [25] These criteria apply whether informed consent is being obtained for a clinical service or for participation in research. There is some guidance in the literature regarding informed consent for genetic services [26-32] and for human subjects research both generally [33] and with specific reference to genetic research. [34,35]
Obstacles to Informed Consent
Much has been written about both participant and medical professional impediments to achieving adequate informed consent. [36,37] One such obstacle results from the imbalance of power inherent in the relationship between participants and medical professionals. Participants often feel intimidated in the face of the authority of the professional and, if they are ill, feel vulnerable as a result of their illness. [38]
There are other barriers that are particularly relevant to consent for cancer susceptibility testing. Obstacles to ensuring participant understanding include variability in the participant's experience with cancer and inherent difficulties in understanding probabilistic information. [39] Obstacles to ensuring that participants are substantially noncontrolled include the unwillingness of some participants to assume an active role in decision making, [40] their often unquestioned trust in the health care system and in their medical professionals, pressure by family members or medical professionals, and financial incentives or constraints due to the cost of care and the status of their insurance coverage. Obstacles to medical professionals' assisting participants in understanding genetic information include their own lack of genetics knowledge, [20,22] their inadequacy at communicating probabilistic information, their cynicism about the validity of the informed consent process, [41,42] and their tendency to be directive. [43,44]
Cross-Cultural/Ethnic Differences
Adequate informed consent in a pluralistic society requires that medical professionals be sensitive to the educational, linguistic, and religious differences among participants and between medical professionals and participants. [45] Medical professionals also must recognize the potential impact of sex, race, ethnicity, class, and culture on the decision-making process. [46-49] For example, there is evidence that Ashkenazi Jewish women have different reactions than African-American women regarding the availability of breast cancer susceptibility testing and their familial obligations if the test is positive. [50] Knowledge of ethnocultural values, beliefs, health practices, and communication styles is fundamental for the effective provision of genetic services. [51] In recent years, the genetic counseling community has published extensively on the topic of cross-cultural counseling. [52-55] The involvement of a community advisory group could assist medical professionals in the planning and conducting of genetic testing protocols. [56]
PROCESS OF INFORMED CONSENT
In this section, we recommend that informed consent be an ongoing process and that medical professionals and participants become partners in decision making. This presupposes that the medical professional is sufficiently informed regarding genetics or knows how to obtain the necessary factual genetics information. We describe the counseling and education components of this process in greater detail.
Process of Decision Making
It is a challenge in complex decision making to respect both the ideal of informed consent and the constraints of the clinical and research environments. Informed consent can be conceptualized in at least 2 ways: the "event model" and the "process model." [57] In the event model, the participant is presented with several options from which to choose, the medical professional usually indicates what he or she thinks is in the participant's best interest, and the participant has the opportunity to agree with or reject the medical professional's advice.
The event model documents informed consent through the completion of a written form summarizing the proposed medical intervention that has been presented orally to the participant by the health care provider prior to obtaining consent. The consent form typically carries legal weight, even though it is widely acknowledged that such documents are only as good as the education that precedes them. The event model is limited, however, in that it takes place at a single point in time. Even though this is not how people make complicated decisions, informed consent typically follows the event model in both the clinical and research contexts.
An alternative way to understand informed consent is to adopt a process model of decision making. In contrast to the event model, the process model assumes an ongoing relationship in which medical professionals elicit participants' values as well as disclose their own, and decision making is shared over time. Many adult participants are accustomed to interactive decision making in which they solicit and receive their medical professional's advice. In 1 study of women's attitudes toward informed consent for breast cancer susceptibility testing, most respondents expressed a desire for their medical professional's recommendations. [58,59] Since the decision to undergo genetic testing for cancer susceptibility is complex, the task force believes that informed consent in this context should be approached as a multistep process, and those considering genetic testing must be given every chance to rethink and confirm their final decision. We therefore recommend that, whenever possible, informed consent for cancer susceptibility testing follow a process model. Further, counseling for such testing should be made in the context of dialogue with families and an understanding of relevant community values.
Informed consent, according to a process model, is more than the transmission of information from an active medical professional to a passive participant. Integral to informed, shared decision making about genetic testing is the entire education and counseling process that occurs when someone faces such a choice. [60] Such counseling should be extensive and address personal aspects of the participant's decision. Participants can have powerful reactions to genetic information that do not necessarily reflect the stability or integrity of the participant. Since every participant is unique, it is important for the medical professional to acknowledge the potentially life-altering nature of this information for some participants.
The informed consent process, while intending to help the participant anticipate issues or worries, may generate new concerns for the participant. Sensitivity to the harms as well as the benefits inherent in the informed consent process itself will allow for a more mutually productive relationship between participant and professional. Participants may benefit from referral to a genetic counselor or a physician or nurse with special expertise in this domain for assistance in making a decision that is consistent with their values and needs at the time. Participants who have the opportunity to explore their own motivations and fears through counseling will be better able to hear and understand information that is disclosed during the educational part of the process.
Process of Education: Formats of Disclosure
Because adults have different learning styles, a variety of disclosure procedures have been suggested for improving the consent process. We recommend that the process be adaptive to many styles of disclosure and decision making, and that medical professionals consider using multiple educational formats as described below.
One-on-One Discussions.
The most common method for disclosing information about a medical intervention is via a one-on-one discussion between a medical professional and a participant. There is some evidence that oral discussions of any kind are superior to other forms of information disclosure [61] and that comprehension of information is improved when nonphysicians present the information. [62,63] Regardless of who does the disclosing, understanding seems directly correlated with the amount of time spent with the learner. [64]
Since genetic counselors have specialized training in discussing inherited risk, they are often considered to be the "gold standard" for such discussions. However, as the number of genetic tests increases, it may be unrealistic to expect all individuals to have access to an in-depth discussion with a genetic counselor before the test. Alternative methods of information disclosure need to be explored.
Group Discussions.
Group discussions are another way to disseminate information about inherited susceptibility to cancer. Like one-on-one discussions, group discussions involve contact with a medical professional. They also have the added advantage of peer interaction, which may promote satisfaction and social acceptance. However, group encounters have limitations. Some people are embarrassed about speaking in groups, public disclosure may jeopardize confidentiality, and an individual's specific needs may not be met.
Written Brochures and Pamphlets.
Written brochures or pamphlets are a less costly way to disclose substantive information about inherited cancer risk to participants. Written materials have been shown to improve knowledge about genetic issues [65] but have some obvious limitations-they are not effective for individuals who do not read, they need to be written in a variety of languages with sensitivity to cultural differences, they need to be concise, and they tend to be written for a general readership rather than the specific participant. Nevertheless, such materials can be standardized and reviewed at the convenience of the participant and are generally helpful as a supplemental learning tool.
Videotapes.
Videotapes, by presenting educational material visually, can provide consistent information in a familiar medium and reach marginally literate individuals. They also have the advantage of being repeatable and user controlled without requiring a great deal of time on the part of the medical professional. [66] However, they have not been shown to be successful in all clinical settings [67] and are neither participant-specific nor interactive.
Interactive Videos and Computers.
More innovative and sophisticated computer-based technologies, such as interactive video or CD-ROM, have the additional potential of tailoring the communication process to the particular learning needs of the participant. [68,69] Several features make computers a desirable way to disclose health-related information. They can be effective at educating participants in a variety of settings, [70-79] they are widely accepted by participants of varied age, socioeconomic status, and educational backgrounds, [80-83] and they can provide consistent and accurate information. Computers also can provide rapid feedback about performance to reinforce learning [84] and can be used to assess knowledge and recall. [72] Computers can be used in a private setting at the participant's own pace, which may decrease embarrassment and frustration. Finally, computers can reduce the time that practitioners spend in direct education. [85] Despite the growing use of computers for patient education, they have not been widely used for genetic education. Studies are ongoing to evaluate their efficacy in providing information about inherited susceptibility to breast cancer (M.J.G., unpublished data, 1997).
Strategies for Improving Comprehension.
Simplifying Written Consent Forms.
Medical consent documents are notorious for their complexity. [86-88] Most are written at an 11th-grade level or higher despite the fact that half the US population currently reads at a ninth-grade level or lower, and 20% of adults read below a fifth-grade level. [89] There are many strategies for improving readability, [90] as well as several computer programs for estimating reading level. These programs can be used to measure language variables within specific passages of writing, [89] but because they do not assess comprehension, the reading level of a consent form can be further adjusted after pretesting the document to measure the target audience's comprehension.
Reinforcing With Interactivity.
It is important for the consent process to provide an opportunity for a participant to ask questions and receive answers. The simple act of asking a participant to recall information can lead to significantly better retention of disclosed information than the standard technique of disclosure without such "quizzing." [91] This technique adds about 5 to 10 minutes to the discussion. Such interactivity is particularly suited to consent involving discussion or interactive computer.
Attending to the Timing of Informed Consent.
Ideally, consent for genetic testing should take place in several stages. In the first stage, there would be extensive genetic counseling about risks, benefits, alternatives, and the like. When possible, counseling should be followed by a period of days or weeks before participants make their decision. Waiting can remove the pressure for an immediate decision, improve comprehension (particularly if a consent form is brought home and read at the participant's convenience [92,93]), and result in more meaningful consent. This waiting period should be followed by a second stage, at which time interested participants would provide explicit consent to proceed with genetic testing.
Assessing the Effectiveness of the Consent Process.
A prerequisite of valid consent is that information be adequately disclosed by medical professionals and understood by participants. Medical professionals should attempt to elicit the degree to which participants understand the information that is disclosed. This could be done with the help of a 2-part consent form, [64,94] in which part 2 asks several questions about the information contained in part 1. Feedback should be provided for questions that are answered incorrectly. [95]
Maintaining Confidentiality
To minimize the risk of stigmatization and discrimination, access to genetic information should be limited. Medical professionals should be prudent in their handling of the information. They should inform participants about the importance of confidentiality and familial implications of genetic testing. This discussion may alert participants to the possibility that genetic test results may be requested by third parties such as relatives, insurers, employers, or other physicians. We recommend that genetic test results only be made available to third parties with explicit consent of the participant. The consent process should include a discussion of whether results will be given to anyone other than the participant and safeguards for protecting confidentiality. These safeguards include use of linked identifiers when handling specimens and data, use of a coding sheet that is kept in a secure place and accessible only to the provider, and, in a research context, use of a Certificate of Confidentiality from the US Department of Health and Human Services [96] to protect against subpoenas.
CONTENT OF INFORMED CONSENT
Ideally, the informed consent process should involve an assessment of the participant's prior experiences, beliefs, attitudes, biases, motivations, and existential issues involving the meaning of testing prior to disclosing specific aspects of testing. The following specific content areas can be addressed within the context of the participant's life and current needs.
Purpose of Test
Participants must be clearly informed of the purpose of the genetic test and, if in a research setting, the aims and design of the research project. Currently there are 2 distinct but overlapping purposes of genetic testing for cancer susceptibility mutations: the discovery of new knowledge in the context of research protocols and the identification of personal genetic risk for purposes of medical management in the clinical setting. If the research design includes disclosure of results, the research team must assure that communication of test results be done with the same standard of care that is maintained in the clinical setting.
Practical Aspects of Test
Practical aspects of the testing process include but are not limited to the following: amount of blood to be drawn, pain and bruising that may accompany blood draw, type of analysis to be performed, cost of the analysis, range of possible results that may be obtained, length of time for results to become available, manner in which results will be communicated, how samples will be stored in the laboratory following completion of the analysis, and name and contact information for at least 1 medical professional who can answer questions throughout the testing process. If testing is being performed within a research protocol, the participant should be apprised of any questionnaires or interviews to be included during the course of the testing process.
Interpretation of Results
Participants must understand that, in many circumstances, genetic testing for cancer susceptibility does not involve a test with unambiguous results. Multiple genes, each with numerous mutations, may be associated with a particular type of cancer. Thus, we recommend that informed consent address the variety of cancer etiologies as well as the limitations of the technology to detect mutations. Helping participants anticipate results and what they may mean is complex and involves abstract thinking about probabilities as well as perception of illness and issues of vulnerability.
Predisposing Cancer Gene Test Indicating the Presence of a Known Mutation.
Women from high-risk breast and ovarian cancer families often report anticipating that they will have a mutation. [97] They have grown up fearing the time when they, too, will develop cancer. Thus, the greatest challenge in obtaining informed consent from women in such families may be to ensure that they understand the limited usefulness of genetic test results in making predictions about their own cancer risk. Further, it may be difficult to help them appreciate how little data exist to guide them on the most effective methods to reduce their morbidity and mortality. Men in these families may have assumed that cancer risk was a worry only for women. Helping men to understand that they can also have a mutation, could pass it on to their children, and may have slightly increased risks of specific cancers themselves [98] makes the option of testing more relevant to them. In the case of genetic testing for colon cancer susceptibility, where effective methods to reduce morbidity and mortality may be better understood, [9] it is still important for participants to understand that a mutation is not equivalent to having cancer nor is it a certainty that cancer will develop. Being tested may, in a sense, replace one type of uncertainty with another. Participants should be encouraged to consider what learning a test result may suggest about their current risk reduction and screening activities. Those who test positive should be encouraged to meet with an oncologist and other specialists to discuss a strategy for prevention and screening activities.
Interpreting a positive test result may be more difficult when it is the first mutation detected in a family, although such detection most likely also implies an increased risk of cancer. Participants should be told the limitations of applying penetrance figures from high-risk families to those individuals who have had few or no affected family members. The relevance of population statistics for individuals remains largely unknown. There will be increasing amounts of information on penetrance of specific mutations, but prior to this, participants need to be told of the estimation involved in interpreting risks.
Predisposing Cancer Gene Test Indicating That a Known Mutation Is Not Present.
If an individual tests negative for an inherited mutation that has previously been identified as being associated with cancer in his or her family, that person's risk may be reduced to that of the general population (the person could have other risk factors). Testing in such circumstances is confined to the known mutation rather than involving complete sequencing of a gene or testing of several candidate genes. This is often the type of testing done in hereditary cancer families where multiple family members are affected.
In the event of a true-negative test result, several points should be emphasized in the pretest and posttest counseling: cancer may still occur, the mutation cannot be passed on to children, and familial relationships may still be affected, especially if other family members are found to have a mutation. Cancer risk reduction and screening recommendations relevant to the general population should be discussed.
Predisposing Cancer Gene Test Result Which Is Not Informative.
There are at least 2 circumstances in which a test result will not help with risk assessment. The first occurs when no mutation has been identified in the family. In this case, a test result that does not identify a mutation may be of little value and, thus, indeterminate for cancer risk. Many individuals deciding whether to be tested for a cancer gene will be the first person in the family tested. Without confirmation that a recognizable mutation has caused cancer, a negative test result may not refine one's risk for developing cancer in the future.
Follow-up for a negative test in this circumstance needs to be anticipated and negotiated with the participant in the consent process. Depending on the status of research findings, future testing may be indicated. In the case of breast cancer susceptibility testing, for instance, if BRCA1 gene sequencing does not identify a mutation in an individual from a high-risk family, offering BRCA2 testing may be warranted depending on the cancer history of the family.
Another reason a test result is classified as indeterminate is if a sequence variation has been identified in the family or individual, but there is insufficient research to know whether the particular variation constitutes a mutation posing an increased risk of cancer or a normal variant (polymorphism) with no associated increased risk. In such cases, provision of cancer risk information may not be possible. If available, further laboratory tests would need to be conducted before determining the clinical significance of the results. Individuals should be apprised about which test will be performed or whether they will need to wait for further technologic advances before such testing is possible.
Psychological and Social Implications
Psychological Implications.
Participants should be informed of potential adverse responses in those found to be mutation carriers such as anxiety, depression, anger, and feelings of vulnerability. In addition, participants may experience guilt over the possibility of having passed the mutation to offspring. Participants who find they are not mutation carriers may also experience guilt if other close family members are found to carry the mutation-so-called survivor guilt. Those who are not mutation carriers may experience regrets if they have made major life decisions, such as prophylactic surgery, based on their perception of risk prior to testing. Individuals who decline testing or who do not receive definitive results may experience persistent anxiety over their risk status.
The short-term and long-term psychological effects of genetic testing for susceptibility to cancer and other adult-onset diseases are not fully known. Potential positive responses include relief from uncertainty, an increased feeling of control as well as joy, and stronger motivation to pursue additional screening or early detection measures. Serious adverse psychological effects do not appear to be common, [14,99,100] although the research is limited. Despite these reassuring preliminary reports, many individuals experience some degree of psychological distress [101] in response to genetic testing for cancer susceptibility. [102,103]
Insurance Risks.
There are substantial market and regulatory differences between health, life, and disability insurances. Insurance discrimination based on genetic test results has been a major concern for state and federal governments, the National Center for Human Genome Research (now the National Human Genome Research Institute), the insurance industry, professional and lay societies, and scholarly commentators. [104-113] Participants should be informed that genetic testing for cancer susceptibility may limit their ability to obtain health, life, or disability insurance, may lead to limitations in coverage, or may result in higher premiums for insurance products. At present, insurers do not themselves conduct genetic testing of applicants, although they are likely to be quite interested in knowing the test results of applicants who are tested elsewhere. Participants should be informed that insurance providers may gain access to their genetic test results through their physician's records, hospital records, or disclosure by the participant in an insurance application process. Participants who provide false information to insurance companies are at risk for policy cancellation or for legal prosecution for insurance fraud.
Whether individuals are at risk for these adverse outcomes will depend on a number of factors. Participants who are at greatest risk of insurance discrimination are those who might undergo individual underwriting for a policy, and those who attempt to change coverage providers. In the private market, 85% to 90% of health policies are purchased through large groups that do not require individual underwriting. [107] In contrast, life insurance is obtained largely through individual policies with approximately 71% of policies purchased on an individual basis in 1989. [109]
The incidence of insurance discrimination based on genetic information has been difficult to document. [114] A growing number of states have passed legislation to restrict health insurance discrimination based on genetic testing. [106,110] However, this type of legislation does not cover many individuals who have insurance provided by a self-insured employer. Passage of the Health Insurance Portability and Accountability Act of 1996 (the Kennedy-Kassebaum bill), stating that no one can be denied insurance for a preexisting condition, [111] demonstrates growing attention to this problem on a national level. However, its effectiveness in protecting individuals with inherited predispositions still needs to be determined. It is appropriate, therefore, to provide detailed information to all participants about the potential for insurance discrimination, paying attention to individual circumstances.
Employment Discrimination.
Participants should be informed that genetic testing may pose a risk to their present or future employment. The magnitude of this risk is unknown. Federal legislation provides some protection against discrimination in the workplace. The Rehabilitation Act of 1973 and the Americans With Disabilities Act of 1990 (ADA) prohibit employment discrimination against those with disabilities or against those who are considered to have a disability, unless the disability precludes performance of the job. [115,116] In 1995, the Equal Employment Opportunity Commission issued a ruling that the definition of disability covers individuals at risk for future health problems based on genetic abnormalities. [117] This interpretation has not been tested in the courts, so the strength of protection provided by the ADA is uncertain. Insurance companies are not regulated under the ADA. While an employer may be prohibited from denying employment to the applicant, he or she may limit or exclude insurance coverage for the employee. Thus, an individual may be effectively barred from a job because of limits placed on insurance benefits associated with the employment.
Options for Medical Follow-up
Although some individuals will seek genetic testing primarily to reduce uncertainty and attendant anxiety, the major motivation for offering and obtaining genetic testing is the hope that medical management following a positive test result can help reduce cancer morbidity and mortality. Participants must be informed of the limits of current knowledge with respect to the treatment, prevention, or early detection of disease based on genetic test results. In general, interventions to reduce morbidity and mortality attributable to cancer can be broken down into 3 categories: (1) risk reduction, including lifestyle changes and prophylactic surgical interventions; (2) early detection interventions; and (3) chemoprevention research on the use of dietary and synthetic agents to block or interrupt the process of carcinogenesis. While epidemiologic research has suggested that dietary and lifestyle factors may be associated with risk for some types of cancer (for example, dietary fat intake and colorectal cancer), the data for specific cancers or specific interventions, even in the general population, are lacking [9] and no such data exist for genetically at-risk individuals. [118]
Privacy and Confidentiality
Medical professionals should not only make every effort to maintain participant confidentiality (see "Maintaining Confidentiality," above), but should explicitly discuss these efforts prior to testing. They should describe the mechanisms for keeping information secure, identify people who might have access to the information, and explain that breaches of confidentiality may occur as a result of who is given information by the participant. Participants also will need to consider whether they wish to share this information with relatives and other medical professionals. Some relatives may not be aware of their family history, and notifying them of their risk may change their sense of privacy or psychosocial well-being. [119] Although such disclosure may be important for the relative, it may pose risks to the participant.
Tissue Storage and Reuse
A unique issue in genetic testing is the ability to store tissue for future testing that is unanticipated at the time the sample is obtained. There have been a number of consensus statements on this issue. [120-122] The medical professional should assure participants that no additional testing on identifiable samples will be done without separate informed consent. Specific consent should be obtained from the participants if samples are to be made anonymous and retained for future research. The length of storage should also be discussed.
Alternatives
An essential element of the informed consent process is the description of alternatives that may be relevant to the participant's decision to participate. One alternative is to forgo testing altogether, since risk assessments can be made on the basis of clinical history without testing. Raising this option acknowledges the experimental and discretionary nature of testing. Options for obtaining testing through other research protocols or clinical programs and the pros and cons of other options should be outlined. Conversely, medical professionals should inform individuals if relevant research protocols are available.
RECOMMENDATIONS FOR FUTURE RESEARCH ON PRETEST INFORMED CONSENT
Genetic research offers substantial promise for the prevention and treatment of cancer. At the present time, the emerging ability to test for cancer susceptibility requires that longer-term prospective research be conducted to better define the utility and applicability of genetic testing in higher and lower risk individuals in the population. As a component of this work, the efficacy of current preventive and early detection strategies must be assessed in men and women at increased risk. Further, additional epidemiologic, behavioral, and ethnographic research is needed to better inform the content and process of pretest education and counseling. We need more answers to questions regarding the nature and number of mutations involved (heterogeneity), the cancer risks associated with mutations (penetrance), and the types and severity of associated cancers (expressivity). Persons with mutations or at high risk should be informed regarding the availability of clinical trials, if appropriate. Research should also pay more attention to understanding psychological responses to testing in terms of their nature and timing, as well as how to identify those individuals at greatest risk of serious adverse effects. In addition, efforts should be made to assess the impact of cancer susceptibility testing on family relationships; extent and impact of insurance and employment discrimination; impact of testing children and adolescents, as well as how and whether the informed consent process should differ for children and adolescents; and impact of culture-based testing (eg, among Ashkenazi Jews) on perceived social obligation to participate in research protocols, as well as social stigma. We must also evaluate various formats for information disclosure and counseling including their provision by different health care professionals. Finally, we must learn whether pretest education and counseling are effective at helping participants understand the meaning of positive and negative test results, whether more effective for some participants than others, whether and when participants want their providers to make recommendations about testing, and what accounts for differences in efficacy of counseling and style of decision making.
The work of the CGSC was supported by the National Human Genome Research Institute, the National Cancer Institute, the National Institute for Nursing Research, and the National Institute for Mental Health.
The authors gratefully acknowledge the organization of the CGSC by Elizabeth Thomson, MS, RN; the helpful comments of the other Consortium members including Deborah Bowen, PhD, Wylie Burke, MD, PhD, Bonnie J. Flick, MD, Judy Garber, MD, MPH, Karen Glanz, PhD, MPH, Ellen R. Gritz, PhD, Don Hadley, MS, Caryn Lerman, PhD, Kenneth Offit, MD, MPH, Gloria M. Petersen, PhD, and Kathryn M. Taylor, PhD; and the suggestions of Consortium consultants including Ellen Wright Clayton, MD, JD, Neil A. Holtzman, MD, MPH, and Karen Rothenberg, JD.
Reprints: Gail Geller, ScD, Johns Hopkins University School of Medicine, 550 N Broadway, Suite 511, Baltimore, MD 21205.
REFERENCES
1. Levine AJ. The genetic origins of neoplasia. JAMA. 1995;273:592. [Fulltext Link] [Medline Link] [CINAHL Link] [Context Link]
2. Rowley JD, Aster JC, Sklar J. The clinical applications of new DNA diagnostic technology on the management of cancer patients. JAMA. 1993;270:2331-2337. [Fulltext Link] [Medline Link] [Context Link]
3. Liu B, Parsons RE, Hamilton SR, et al. hMSH2 mutations in hereditary nonpolyposis colorectal cancer kindreds. Cancer Res. 1994;54:4590-4594. [Medline Link] [Context Link]
4. Papadopoulas N, Nicolaides NC, Wei Y-F, et al. Mutation of a mutL homolog in hereditary colon cancer. Science. 1994;263:1625-1629. [Medline Link] [Context Link]
5. Nicolaides NC, Papadopoulas N, Liu B, et al. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature. 1994;371:75-80. [Medline Link] [Context Link]
6. Miki Y, Swensen J, Shattuck-Eidens D, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266:66-71. [Fulltext Link] [Medline Link] [Context Link]
7. Wooster R, Neuhausen SL, Mangion J, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science. 1994;265:2088-2090. [Fulltext Link] [Medline Link] [Context Link]
8. Malkin D, Li FP, Strong LC, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas and other neoplasms. Science. 1990;250:1233-1238. [Medline Link] [Context Link]
9. Burke W, Petersen G, Lynch P, et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer, I: hereditary nonpolyposis colon cancer. JAMA. 1997;277:915-919. [Fulltext Link] [Medline Link] [Context Link]
10. Burke W, Daly M, Garber J, et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer, II: BRCA1 and BRCA2. JAMA. 1997;277:997-1003. [Fulltext Link] [Medline Link] [Context Link]
11. National Advisory Council for Human Genome Research. Statement on use of DNA testing for presymptomatic identification of cancer risk. JAMA. 1994;271:785. [Medline Link] [CINAHL Link] [Context Link]
12. Garber JE, Schrag D. Testing for cancer susceptibility. JAMA. 1996;275:1928-1929. [Fulltext Link] [Medline Link] [Context Link]
13. Li FP, Garber JE, Friend SH, et al. Recommendations on predictive testing for germ line p53 mutations among cancer-prone individuals. J Natl Cancer Inst. 1992;84:1156-1160. [Medline Link] [Context Link]
14. Lerman C, Narod S, Schulman K, et al. BRCA1 testing in families with hereditary breast-ovarian cancer: a prospective study of patient decision making and outcomes. JAMA. 1996;275:1885-1892. [Fulltext Link] [Medline Link] [Context Link]
15. Statement of the American Society of Human Genetics on genetic testing for breast and ovarian cancer predisposition. Am J Hum Genet.1994;55:i-iv. [Context Link]
16. Presymptomatic genetic testing for heritable breast cancer risk. Press release of the National Breast Cancer Coalition. Washington, DC, September 28, 1995. [Context Link]
17. Kahn P. Coming to grips with genes and risk. Science. 1996;274:496-498. [Medline Link] [Context Link]
18. Geller G, Kass NE. Informed consent in the context of prenatal HIV screening. In: Faden RR, Geller G, Powers GM, eds. AIDS, Women and the Next Generation: Towards a Morally Acceptable Public Policy on HIV Screening of Pregnant Women and Newborns. New York, NY: Oxford University Press; 1991. [Context Link]
19. Garber JE, Patenaude AF. Ethical, social and counselling issues in hereditary cancer susceptibility. Cancer Surv. 1995;25:381-397. [Medline Link] [Context Link]
20. Lippman A. Prenatal genetic testing and screening: constructing needs and reinforcing inequities. Am J Law Med. 1991;17:15-50. [Medline Link] [Context Link]
21. Hofman KA, Tambor ES, Chase GA, Geller G, Faden RR, Holtzman NA. Physicians' knowledge of genetics and genetic tests. Acad Med. 1993;68:625-632. [Medline Link] [Context Link]
22. Lee JM. Screening and informed consent. N Engl J Med. 1993;328:438-440. [Fulltext Link] [Medline Link] [Context Link]
23. Holtzman NA. Are we ready to screen for inherited susceptibility to cancer? Oncology. 1996;10:57-64. [Medline Link] [Context Link]
24. ASHG/ACMG Report. Points to consider: ethical, legal and psychosocial implications of genetic testing in children and adolescents. Am J Hum Genet. 1995;57:1233-1241. [Medline Link] [Context Link]
25. Appelbaum PS, Lidz CW, Meisel A. Informed Consent: Legal Theory and Clinical Practice. New York, NY: Oxford University Press; 1987. [Context Link]
26. Faden RR, Beauchamp TL, King NP. A History and Theory of Informed Consent. New York, NY: Oxford University Press, 1986:86. [Context Link]
27. Elias S, Annas GJ. Generic consent for genetic screening. N Engl J Med. 1994;330:1611-1613. [Fulltext Link] [Medline Link] [CINAHL Link] [Context Link]
28. Andrews LB, Fullarton JE, Holtzman NA, Motulsky AG. Assessing Genetic Risks: Implications for Health and Social Policy. Washington, DC: National Academy Press; 1994:259-282. [Context Link]
29. Press N, Browner CH. Risk, autonomy, and responsibility: informed consent for prenatal testing. Hastings Cent Rep. 1995;25:S9-S12. [Medline Link] [Context Link]
30. Marteau TM. Towards informed decisions about prenatal testing: a review. Prenat Diagn. 1996;14:1215-1226. [Context Link]
31. Holtzman NA, Faden RR, Chwalow JA, Horn SD. Effect of informed consent on mothers' knowledge of newborn screening. Pediatrics. 1983;72:807-812. [Medline Link] [Context Link]
32. Sharp NF. Informed consent and Huntington disease: a model for communication. Am J Med Genet. 1994;50:239-246. [Medline Link] [Context Link]
33. President's Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Washington, DC: Public Health Service; 1979. [Context Link]
34. President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. The Ethical and Legal Implications of Informed Consent in the Patient-Practitioner Relationship. Washington, DC: US Government Printing Office; 1982;1:74-76. [Context Link]
35. Andrews LB. Regulation of genetic research in humans. In: Medical Genetics: A Legal Frontier. Chicago, Ill: American Bar Foundation; 1987:38-41. [Context Link]
36. Office of Protection From Research Risks. Protecting Human Research Subjects: Institutional Review Board Guidebook. Bethesda, Md: National Institutes of Health; 1993:42-63. [Context Link]
37. Kent G. Shared understandings for informed consent: the relevance of psychological research on the provision of information. Soc Sci Med. 1996;43:1517-1523. [Medline Link] [CINAHL Link] [Context Link]
38. Katz J. The Silent World of Doctor and Patient. New York, NY: Free Press; 1984. [Context Link]
39. Mazur DJ. Why the goals of informed consent are not realized: treatise on informed consent for the primary care physician. J Gen Intern Med. 1988;3:370-379. [Medline Link] [Context Link]
40. Lidz CW, Meisel A, Osterweis M, Holden JL, Marx JH, Munetz MR. Barriers to informed consent. Ann Intern Med. 1983;99:539-543. [Medline Link] [Context Link]
41. Katz J. Why doctors don't disclose uncertainty. Hastings Cent Rep. 1984;38:35-44. [Medline Link] [Context Link]
42. Taylor KM, Kelner M. Informed consent: the physician's perspective. Soc Sci Med. 1987;24:135-143. [Medline Link] [Context Link]
43. Carter MA. Patient-provider relationship in the context of genetic testing for hereditary cancers. J Natl Cancer Inst Monogr. 1995;17:119-121. [Medline Link] [Context Link]
44. Geller G, Tambor ES, Chase GA, Hofman KJ, Faden RR, Holtzman NA. Incorporation of genetics into primary care practice: will physicians do the counseling and will they be directive? Arch Fam Med. 1993;2:1119-1125. [Medline Link] [Context Link]
45. Lidz CW, Applebaum P, Meisel A. Two models of implementing informed consent. Arch Intern Med. 1988;148:1385-1389. [Medline Link] [Context Link]
46. Asch A, Geller G. Feminism, bioethics and genetics. In: Wolf S, ed. Feminism and Bioethics: Beyond Reproduction. New York, NY: Oxford University Press; 1996. [Context Link]
47. Betancourt H, Lopez SR. The study of culture, ethnicity, and race in American psychology. Am Psychol. 1993;48:629-637. [Context Link]
48. Gostin LO. Informed consent, cultural sensitivity, and respect for persons. JAMA. 1995;274:844-845. [Fulltext Link] [Medline Link] [CINAHL Link] [Context Link]
49. Carrese J, Rhodes LA. Western bioethics on the Navajo reservation: benefit or harm? JAMA. 1995;274:826-829. [Fulltext Link] [Medline Link] [Context Link]
50. Geller G, Bernhardt BA, Helzlsouer KA, Holtzman NA, Stefanek MM, Wilcox PM. Informed consent and BRCA1 testing. Nat Genet. 1995;11:364. [Medline Link] [Context Link]
51. Wang V, Marsh FH. Ethical principles and cultural integrity in health care delivery: Asian ethnocultural perspectives in genetic services. J Genet Couns. 1992;1:81-92. [Context Link]
52. Wang WO. Cultural competency in genetic counseling. J Genet Couns. 1994;3:267-277. [Context Link]
53. Punales-Morejon D, Rapp R. Ethnocultural diversity and genetic counseling training: the challenge for a twenty-first century. J Genet Couns. 1993;2:155-158. [Context Link]
54. Weil J, Mittman I. A teaching framework for cross-cultural genetic counseling. J Genet Couns. 1993;2:159-169. [Context Link]
55. Dixson B, Dang V, Cleveland JO, Peterson RM. An education program to overcome language and cultural barriers to genetic services. J Genet Couns. 1992;1:267-274. [Context Link]
56. Botkin J, Croyle RT, Smith KR, et al. A model protocol for evaluating the behavioral and psychosocial effects of BRCA1 testing. J Natl Cancer Inst. 1996;88:872-882. [Medline Link] [Context Link]
57. Rosoff AJ. Informed Consent: A Guide for Health Care Providers. Rockville, Md: Aspen Publications; 1981. [Context Link]
58. Bernhardt BA, Geller G, Strauss M, et al. Towards a model informed consent process: a qualitative assessment of women's attitudes about genetic testing for breast cancer risk. J Genet Couns. In press. [Context Link]
59. Geller G, Strauss M, Bernhardt BA, Holtzman NA. 'Decoding' informed consent: insights from women regarding genetic testing for breast cancer susceptibility. Hastings Cent Rep. 1997;27:28-33. [Medline Link] [Context Link]
60. Singer GGS. Clarifying the duties and goals of genetic counselors: implications for nondirectiveness. In: Gert B, Berger EM, Cahill GF, et al, eds. Morality and the New Genetics: A Guide for Students and Health Care Providers. Sudbury, Mass: Jones & Bartlett Publishers Inc; 1996. [Context Link]
61. Allen KD, Hodges ED, Knudsen SK. Comparing four methods to inform parents about child behavior management: how to inform for consent. Pediatr Dent. 1995;17:180-186. [Medline Link] [Context Link]
62. Muss HB, White DR, Michielutte R, et al. Written informed consent in patients with breast cancer. Cancer. 1979;43:1549-1556. [Medline Link] [Context Link]
63. Dodd MJ, Mood DW. Chemotherapy: helping patients to know the drugs they are receiving and their possible side effects. Cancer Nurs. 1981;4:311-318. [Medline Link] [Context Link]
64. Silva MC, Sorrell JM. Enhancing comprehension of information for informed consent: a review of empirical research. IRB. 1988;10:1-5. [Context Link]
65. Faden RR, Chwalow AJ, Orel-Crosby E, Holtzman NA, Chase GA, Leonard CO. What participants understand about a maternal serum alpha fetoprotein screening program. Am J Public Health. 1985;75:1381-1384. [Medline Link] [CINAHL Link] [Context Link]
66. Barbour GL, Blumenkrantz MJ. Videotape aids informed consent decision. JAMA. 1978;240:2741-2742. [Medline Link] [Context Link]
67. Westreich L, Levine S, Ginsburg P, Wilets I. Patient knowledge about electroconvulsive therapy: effect of an informational video. Convuls Ther. 1995;11:32-37. [Medline Link] [Context Link]
68. Kasper JF, Mulley AG, Wennberg JE. Developing shared decision-making programs to improve the quality of health care. QRB Qual Rev Bull. 1992;18:183-190. [Medline Link] [CINAHL Link] [Context Link]
69. Hopper KD, Zajdel M, Hulse SF, et al. Interactive method of informing patients of the risks of intravenous contrast media. Radiology. 1994;192:67-71. [Medline Link] [Context Link]
70. Wetstone SL, Sheehan TJ, Votaw RS, Peterson MG, Rothfield N. Evaluation of a computer based education lesson for patients with rheumatoid arthritis. J Rheumatol. 1985;12:907-912. [Medline Link] [Context Link]
71. Smith JM, Pike RA, Jakubowski B, Pardoe JR. Survey of computer programs for diabetes management and education. Diabetes Educ. 1988;14:412-415. [Medline Link] [CINAHL Link] [Context Link]
72. Kumar NB, Bostow DE, Schapira DV, Kritch KM. Efficacy of interactive, automated programmed instruction in nutrition education for cancer prevention. J Cancer Educ. 1993;8:203-211. [Medline Link] [Context Link]
73. Gustafson DH, Bosworth K, Hawkins RP, Boberg EW, Bricker E. CHESS: a computer-based system for providing information, referrals, decision support and social support to people facing medical and other health related crises. In: Firese ME, ed. Sixteenth Annual Symposium on Computer Applications in Medical Care. New York, NY: McGraw-Hill; 1993:161-165. [Context Link]
74. Slack WV, Hicks GP, Reed CE, Van Cura LJ. A computer-based medical history system. N Engl J Med. 1966;274:194-198. [Medline Link] [Context Link]
75. Slack WV, Slack CW. Patient-computer dialogue. N Engl J Med. 1972;286:1304-1309. [Medline Link] [Context Link]
76. Tibbles L, Lewis C, Reisine S, Rippey R, Donald M. Computer-assisted instruction for preoperative and postoperative patient education in joint replacement surgery. Comput Nurs. 1992;10:208-212. [Medline Link] [CINAHL Link] [Context Link]
77. Leirer VO, Morrow DG, Pariante GM, Sheikh JI. Elders' nonadherence, its assessment, and computer-assisted instruction for medication recall training. J Am Geriatr Soc. 1988;36:877-884. [Medline Link] [Context Link]
78. Slack W. Patient counseling by computer. In: Zoog S, Yarnall S, eds. The Changing Health Care Team: Improving Effectiveness in Patient Care. Seattle, Wash: Medical Communications and Services Assoc; 1976:108-111. [Context Link]
79. Ghosh A, Greist JH. Computer treatment in psychiatry. Psychiatr Ann. 1988;18:246-250. [Context Link]
80. Kahn G. Computer-based patient education: a progress report. MD Comput. 1993;10:93-99. [Medline Link] [CINAHL Link] [Context Link]
81. Gillispie MA, Ellis LBM. Computer-based patient education revisited. J Med Syst. 1993;17:119-125. [Medline Link] [Context Link]
82. Kinzie MB, Schorling JB, Siegel M. Prenatal alcohol education for low-income women with interactive multimedia. Patient Educ Couns. 1993;21:51-60. [Medline Link] [CINAHL Link] [Context Link]
83. Kulik CC, Kulik JA. Effectiveness of computer-based instruction: an updated analysis. Comput Hum Behav. 1991;7:75-94. [Context Link]
84. Price RV. Computer-Aided Instruction: A Guide for Authors. Pacific Grove, Calif: Brooks/Cole Publishing Co; 1991. [Context Link]
85. Blackwell M, Niemiec R, Walberg H. CAI can be doubly effective. Phi Delta Kappa. 1986;67:750-751. [Context Link]
86. Philipson SJ, Doyle MA, Gabram SGA, Nightingale C, Philipson EH. Informed consent for research: a study to evaluate readability and processability to effect change. J Invest Med. 1995;43:459-467. [Medline Link] [Context Link]
87. Hopper KD, TenHave TR, Hartzel J. Informed consent forms for clinical and research imaging procedures: how much do patients understand? AJR Am J Roentgenol. 1995;164:493-496. [Medline Link] [Context Link]
88. Grundner TM. On the readability of surgical consent forms. N Engl J Med. 1980;302:900-902. [Medline Link] [Context Link]
89. Meade CD, Howser DM. Consent forms: how to determine and improve their readability. Oncol Nurs Forum. 1992;19:1523-1528. [Medline Link] [CINAHL Link] [Context Link]
90. Doak CC, Doak LG, Root JH. Teaching Patients With Low Literacy Skills. Philadelphia, Pa: JB Lippincott; 1996. [Context Link]
91. White CS, Mason AC, Feehan M, Templeton PA. Informed consent for percutaneous lung biopsy: comparison of two consent protocols based on patient recall after the procedure. AJR Am J Roentgenol. 1995;165:1139-1142. [Medline Link] [Context Link]
92. Morrow G, Gootnick J, Schmale A. A simple technique for increasing cancer patients' knowledge of informed consent to treatment. Cancer. 1978;42:793-799. [Medline Link] [Context Link]
93. Bernhardt BA, Chase GA, Faden RR, et al. Educating patients about cystic fibrosis carrier screening in a primary care setting. Arch Fam Med. 1996;5:336-340. [Fulltext Link] [Medline Link] [Context Link]
94. Miller R, Willner HS. The two-part consent form: a suggestion for promoting free and informed consent. N Engl J Med. 1974;290:964-965. [Medline Link] [Context Link]
95. Taub HA, Baker MT. A reevaluation of informed consent in the elderly: a method for improving comprehension through direct testing. Clin Res. 1984;32:17-21. [Medline Link] [Context Link]
96. Early CL, Strong LC. Certificate of confidentiality: a valuable tool for protecting genetic data. Am J Hum Genet. 1995;57:727-731. [Medline Link] [Context Link]
97. Biesecker BB, Boehnke M, Calzone K, et al. Genetic counseling for families with inherited susceptibility to breast and ovarian cancer. JAMA. 1993;269:1970-1974. [Fulltext Link] [Medline Link] [CINAHL Link] [Context Link]
98. Smith JR, Freije D, Carpten JD, et al. Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search. Science. 1996;274:1371-1374. [Fulltext Link] [Medline Link] [Context Link]
99. Croyle R, Smith K, Botkin J, Baty B, Nash J. Psychological responses to BRCA1 mutation testing: preliminary findings. Health Psychol. 1997;16:63-72. [Medline Link] [Context Link]
100. Wiggins S, Whyte P, Huggins M, et al. The psychological consequences of predictive testing for Huntington's disease. N Engl J Med. 1992;327:1401-1405. [Medline Link] [Context Link]
101. Huggins M, Bloch M, Wiggins S, et al. Predictive testing for Huntington disease in Canada: adverse effects and unexpected results in those receiving a decreased risk. Am J Med Genet. 1992;42:508-515. [Medline Link] [Context Link]
102. Lynch HT, Watson P, Conway TA, et al. DNA screening for breast/ovarian cancer susceptibility on linked markers: a family study. Arch Intern Med. 1993;153:1979-1987. [Medline Link] [Context Link]
103. Lerman C, Daly M, Masny A, Balshem A. Attitudes about genetic testing for breast-ovarian cancer susceptibility. J Clin Oncol. 1994;12:843-850. [Medline Link] [Context Link]
104. US Congress Office of Technology Assessment. Genetic Tests and Health Insurance: Results of a Survey: Background Paper. Washington, DC: US Government Printing Office; October 1992. Publication OTA-BP-BA-98. [Context Link]
105. NIH-DOE Working Group on Ethical Legal, and Social Implications of Human Genome Research. Genetic Information and Health Insurance: Report of the Task Force on Genetic Information and Health Insurance. Washington, DC: US Dept of Health and Human Services; May 1993. NIH publication 93-3686. [Context Link]
106. Brown RS, Marshall K. Advances in Genetic Information: A Guide for State Policy Makers. 2nd ed. Lexington, Ky: Council of State Governments; 1993. [Context Link]
107. American Council of Life Insurance and The Health Insurance Association of America. Report of the ACLI-HIAA Task Force on Genetic Testing. Washington, DC: American Council of Life Insurance; 1991. [Context Link]
108. Hudson KL, Rothernberg KH, Andrews LB, Kahn MJ, Collins F. Genetic discrimination and health insurance: an urgent need for reform. Science. 1995;270:391-393. [Fulltext Link] [Medline Link] [Context Link]
109. Ostrer H, Allen W, Crandall LA, et al. Insurance and genetic testing: where are we now? Am J Hum Genet. 1993;52:565-577. [Medline Link] [Context Link]
110. Rothstein MA. Genetics insurance, and the ethics of genetic counseling. In: Molecular Genetic Medicine. Vol 3. Orlando, Fla: Academic Press Inc; 1993:159-177. [Context Link]
111. Health Insurance Portability and Accountability Act of 1996. Pub L No. 104-191, 110 Stat 1936. [Context Link]
112. Hereditary Susceptibility Working Group of the National Action Plan on Breast Cancer. Commentary on ASCO (American Society of Clinical Oncology) statement on genetic testing for cancer susceptibility. J Clin Oncol. 1996;14:1738-1740. [Context Link]
113. American Society of Clinical Oncology. Genetic testing for cancer susceptibility. J Clin Oncol. 1996;14:1730-1736. [Medline Link] [CINAHL Link] [Context Link]
114. Lapham EV, Kozma C, Weiss JO. Genetic discrimination: perspectives of consumers. Science. 1996;274:621-624. [Fulltext Link] [Medline Link] [Context Link]
115. McEwen JE, Reilly PR. State legislative efforts to regulate use and potential misuse of genetic information. Am J Hum Genet. 1992;51:637-647. [Context Link]
116. Natowitz MR, Alper JK, Alper JS. Genetic discrimination and the Americans With Disabilities Act. Am J Hum Genet. 1992;51:895-897. [Medline Link] [Context Link]
117. Equal Employment Opportunity Commission. Compliance Manual, vol 1. Washington, DC: Equal Employment Opportunity Commission; March 14, 1995. EEOC order 915.002, section 902. [Context Link]
118. Nixon DW. Status of cancer prevention clinical trials. De Vita VT Jr, Hellman S, Rosenberg SA, eds. Cancer Prevention Update. Philadelphia, Pa: JB Lippincott; 1991:1-9. [Context Link]
119. Winter PR, Wiesner GL, Finnegan J, et al. Notification of a family history of breast cancer: issues of privacy and confidentiality. Am J Med Genet. 1996;66:1-6. [Medline Link] [Context Link]
120. ASHG Board of Directors Report. Statement on informed consent for genetic research. Am J Hum Genet. 1996;59:471-474. [Medline Link] [Context Link]
121. Clayton EW, Steinberg KK, Khoury MJ, et al. Informed consent for genetic research on stored tissue samples. JAMA. 1995;274:1786-1792. [Fulltext Link] [Medline Link] [Context Link]
122. ACMG (American College of Medical Genetics) Storage of Genetic Materials Committee. Statement on storage and use of genetic materials. Am J Hum Genet. 1995;57:1499-1500. [Medline Link] [Context Link]
Disease Susceptibility; Genetic Screening; Genetic Counseling; Informed Consent; Neoplasms
 |
 |
 |
 |