As the healthcare community ushers in the "post genomics" era, many questions surrounding genetic testing, privacy and discrimination arise. One key issue concerns the process of obtaining the informed consent of an individual prior to pursuing genetic testing. This process is meant to empower individuals to make educated and autonomous decisions about genetic testing that are consistent with their individual beliefs and social circumstances.
Healthcare providers can expect to be held to a more stringent standard of informed consent for predictive genetic testing than for symptomatic testing. Indeed, some states have begun adopting regulations for predictive testing. For example, sections 79-1 of the New York Civil Rights Law and 2612 of the New York Insurance Law state that written informed consent is mandatory for all predictive genetic tests.1 Massachusetts has a similar law also requiring written informed consent for predictive testing.2
Of course, many of the psychological and social issues associated with predictive genetic testing also hold true with symptomatic testing and speak to the benefit of obtaining informed consent from both asymptomatic and symptomatic patients. Genetic diagnoses have a broad range of health implications for entire families and potentially carry a stigma that can be emotionally troubling. Providing patients with information about possible outcomes of genetic testing via the informed consent process can significantly ameliorate these concerns for affected individuals and their families.
Normally, regulations requiring informed consent are satisfied by providing a signed document attesting that a particular process has been carried out. However, it is important to note that informed consent is best when it is part of a bilateral educational process involving a dialog of questions and answers between a patient and his/her physician or other health care practitioner. This NeuroCAST™ session presents a hypothetical situation demonstrating some of the concerns of an asymptomatic patient considering a predictive genetic test and how his or her neurologist might handle the informed consent process.
Consider Jane Smith, a twenty-two year old college senior anticipating graduation and marriage within the next few months. Jane is a mature and ambitious young woman who takes a methodical approach to life's decisions. Her plans to pursue a PhD and her recent engagement are based on careful emotional introspection and analysis of her personal ambitions. Despite her meticulous approach, however, Jane feels that she has avoided consideration of a crucial piece of information: a piece of information she feels has the potential to radically alter both her marriage and career plans.
A few years ago, Jane's older brother Paul, an excellent golfer, began to complain that his swing was falling apart. Used to Paul's fixation on the subtle nuances of his technique, his family assumed he was going through a temporary phase that was sure to be resolved by a few holes with a golf pro. When Paul's speech became slurred and he fell down a flight of stairs, Jane and her family realized the problem was far more profound then they had originally suspected and their concern was confirmed by a neurologist's diagnosis of Spinocerebellar Ataxia Type One (SCA1). (SCA1 often presents in a patient's twenties or thirties and is associated with gait ataxia, dysarthria and bulbar dysfunction. The interval between onset and death is from 10 to 30 years.)
When Paul was diagnosed, Jane and her family researched SCA1 and learned that the disease was autosomal dominant, 
i.e., an individual possessing a single copy of the mutation would be affected by the disease. In most cases of autosomal dominant inheritance, affected families members will be seen in every generation. Jane did not know of any other family members affected with SCA1. However, Jane's mother died at a young age and Paul's doctor said that Jane's mother may have possessed an SCA1 mutation but died before the onset of symptoms. Thus, Jane knew that it was possible that she also had inherited an SCA1 mutation.
Jane decides that she must now face this possibility and learn her genetic status. She feels that proceeding with academic and family plans without this information would be unfair to herself, her fiancé and her future children. She comes to see you for predictive SCA1 genetic testing. What do you tell her? What does the law require you to tell her?
A critical component of Jane's care will be the informed consent process, i.e., ensuring that she is making an educated and autonomous decision. To do this, she will need to understand the risks and benefits of genetic testing and how it may impact her family life, career, insurability, and emotional well-being. Further, she will need to know the technical details about the testing process and the clinical significance of results. The Practice Committee Genetics Testing Task Force of the American Academy of Neurology makes the following recommendation:
Before ordering a genetic test for a major neurological disorder, neurologists should ordinarily establish that a patient or lawful surrogate is capable of comprehending relevant disclosures and capable of exercising informed choice. If these conditions exist, the neurologist or collaborating genetic counselor should disclose why the test is recommended, the predictive weight of the test, the potentially adverse consequences of a positive test (e.g., extreme emotional distress, stigmatization, loss of health insurance or employment), the benefits of enhanced knowledge about genotype (whether the test is positive or negative), and any negative consequences of not testing (e.g., transmission of a detectable disease-associated genotype to offspring).3
Assembling the relevant information about a genetic test, communicating this information to a patient, and facilitating a meaningful interaction structured to address the issues relevant to the patient's testing decision can be challenging and time-consuming. For these reasons, many physicians opt to work with genetic counselors particularly for their asymptomatic patients.
(The National Society of Genetic Counselors provides a listing of genetic counselors by geographic location.) Genetic counselors are specifically trained to translate the complex principles of genetics for patients and to assist patients and families in the decision-making process.
Regardless of whether physicians provide technical testing information and emotional support to patients on their own or in collaboration with a genetic counselor, it is important that this interaction occurs prior to testing. Pre-test counseling can ameliorate some of the potential adverse emotional consequences experienced by patients following testing by both preparing an individual to learn his or her test result and establishing rapport between the health care provider and patient.
The New York State Task Force on Life and the Law provides the following description of the informed consent process.4 Please click on topics of interest for more detailed topic descriptions and information specific to Jane Smith's situation.
- Purpose of the test:
- Genetic alteration detected by the assay.
- Disorder associated with the genetic alteration.
- Protocol for completing the test:
- Sample requirement.
- Disclosure of laboratory that will be performing the analysis.
- Expected result date.
- Method by which results will be communicated to the tested individual.
- Potential testing outcomes:
- Clinical significance of positive and negative results.
- Accuracy of testing (risk of false positive and false negative results).
- Testing sensitivity and specificity.
- Capability of test to predict disease severity and age of onset.
- Possibility that test will not modify individual's risk of being affected with the disorder.
- Risks of genetic testing:
- Psychological distress for patient and family.
- Employment and/or insurance discrimination.
- Discovery of additional information beyond tested disease (i.e., non-paternity).
- Benefits of genetic testing:
- Risk status is clarified (resolves uncertainty).
- Family and career planning.
- Voluntariness of testing.
- Alternatives to genetic testing for assessing risk status.
- Confidentiality:
- Assessment of individuals authorized to access test results.
- Post-testing surveillance and disease-treatment options.
- Anticipated cost to patient for genetic counseling and testing.
- Purpose of the test:
DNA will be extracted from Jane's blood sample and tested for the trinucleotide repeat expansion mutation associated with SCA1. The test counts the number of trinucleotide repeats in each copy of an individual's two SCA1 genes. The testing facility will correlate the number of trinucleotide repeats with the expected clinical outcome based upon review of the most current literature on SCA1.
- Protocol for completing the test:
About 10cc of blood will be drawn and sent to an outside laboratory for genetic testing. The assay is typically complete within two weeks. The result will be disclosed in-person during another visit, regardless of whether the result is negative or positive.
- Potential testing outcomes:
As stated above, the number of SCA1 repeats Jane is reported to have will indicate with greater than 99% accuracy whether or not she will develop SCA1. The assay is greater than 99% sensitive and specific for this disorder; in other words, all individuals predisposed to SCA1 will be positive for this assay and a positive result is consistent with no diseases other than SCA1. A false positive or false negative result would only occur if there was a sample switch or other laboratory error (the frequency of such errors is estimated to be less than 1% in general). Individuals with large SCA1 expansion mutations generally have more severe symptoms and an earlier age of onset. However, the repeat number cannot be used with certainty to predict severity and the age of onset in asymptomatic individuals.
- Risks of genetic testing:
Psychological distress for patient and family: Jane has decided that she wants to know her testing status to guide her career and family plans, but has she considered what her emotional reaction would be to a positive or negative result? How would she cope with a positive result? Would she feel "survivor guilt" in the event of a negative result? How will the result impact her plans to have children? Would she consider prenatal diagnosis? How do Jane's family and fiancé view her desire to be tested? Is Jane planning to disclose the test results to her fiancé, family and/or friends? Once these individuals know that Jane is being tested, they will expect to be informed of the result and Jane will need to prepare herself for their questions.
Employment and/or insurance discrimination: Would a positive result preclude her school and/or career plans? Has she considered how a positive result might impact her candidacy for health and life insurance? Would an insurance company regard a positive result as a pre-existing condition?
Discovery of additional information beyond tested disease (i.e., non-paternity): The incidence of non-paternity is about 5-10% of all pregnancies. If the genotype of both of parents is known, test results can potentially reveal non-paternity (if this is the case). Informing a patient that this is a possibility may ameliorate the shock of the information (if non-paternity was discovered) or potentially discourage him or her from testing if the patient has reason to suspect this outcome.
- Benefits of genetic testing:
Risk status is clarified (resolves uncertainty): Ever since her brother's diagnosis, Jane has experienced a great deal of anxiety about her own status. The risk that she has inherited an SCA1 mutation is a heavy weight on her shoulders and she feels that this uncertainty may be harder for her to cope with than a potential positive result would be.
Family and career planning: Jane's sister, like many individuals at-risk of having inherited a genetic mutation for a devastating and non-preventable disease, has decided that she does not want to know her status. Jane feels differently than her sister and feels that knowing her status is necessary to make informed decisions to shape a life consistent with her needs and beliefs.
- Voluntariness of testing:
Jane's choice to pursue testing is a personal decision. She should not be coerced by family members, her health care provider, or any other individual or group of individuals to pursue or refuse testing. Discussing the pressure Jane may feel from her family and fiancé about asymptomatic testing may help her to clarify her motivations for testing and distinguish them from external influences.
- Alternatives to genetic testing for
assessing risk status:
Given that Jane is asymptomatic, there are no medical tests outside of the genetic assay which would revise her risk status. In the case of some genetic diseases associated with trinucleotide repeat expansion mutations, like Huntington Disease, Bayesian calculations can be used to lower an at-risk individual's risk, provided they remain asymptomatic beyond the average age of onset for the disease. SCA1, however, is not very amenable to Bayesian analysis, as the age of onset is not as tightly linked to the number of trinucleotide repeats.
- Confidentiality:
Assessment of individuals authorized to access test results. The referring physician will receive Jane's test results. Other parties may also request copies of the result report depending on the protocol of the reimbursement system and/or medical record department of the health facility where she receives her care. Jane should be made aware of the reporting system to determine whether it is acceptable or if she would prefer to restrict or broaden access to her results.
- Post-testing surveillance and disease-treatment
options:
SCA1 cannot be prevented or cured. If Jane tests positive for an SCA1 mutation, her neurologist may want to establish regular visits to monitor for the onset of symptoms.
- Anticipated cost to patient for genetic counseling
and testing:
What will be the total cost of the testing and pre- and post-test genetic counseling? Insurance coverage is variable and Jane may find that her costs will be covered entirely, partially or not all. If Jane plans to submit an insurance claim, it would be recommended that she contact her company to inquire about prior approval for coverage.
- Resources for physicians:
- Educational resources for patients:
- Lay Advocacy Groups, Support Groups, Information on Genetic Conditions and Birth Defects for Professionals, Educators and Individuals
- Patient brochure on informed decision making in predictive HD testing
- Patient brochure on informed decision making in predictive DM testing
- Patient brochure on informed decision making in predictive ataxia testing
- Athena Diagnostics' genetic counselor, Anne R. Yesley, MS, is available to answer questions health care practitioners may have about informed consent.
- Email: ayesley@athenadiagnostics.com
- Phone: 800-394-4493 ext. 3021
