Informed Consent Process in Alpha-1 Testing of At-Risk Children: Views of Parents and Adults Tested as Children

Abstract

Targeted testing programs are identifying increasing numbers of adults affected by Alpha-1 Antitrypsin Deficiency (Alpha-1) who are making decisions about genetic testing for their at-risk children. Although there are possible benefits, there are also potential risks. The purpose of this pilot study was to explore attitudes toward testing at-risk children from the first hand perspective of those involved, identify the benefits and risks experienced therein, and compare the views of parents and adults tested as children (ATC). The results of this pilot study suggest that ATC were significantly more favorable to including children in testing decisions than parents. ATC strongly indicated that they want to be involved in the testing decision and give permission prior to testing (p = 0.007). While the majority of ATC and parents were in favor of newborn screening for Alpha-1, parents had more extreme views, both positive and negative (p = 0.04). Both ATC and parents expressed significantly higher likelihoods of possible risks and benefits following Alpha-1 testing than they actually experienced. Results do not reveal serious harms from testing at-risk children. The two groups indicated that they want information regarding access to insurance, inheritance and expression, impact on anxiety, association with smoking, and usefulness in future planning prior to a decision to test or not to test at risk children. From the resulting data and ethical analysis we recommend that parents and children have relevant information prior to testing for Alpha-1 and that at risk children are directly involved in the decision-making process prior to testing.

Keywords: :

• Alpha-1 Antitrypsin Deficiency
• Genetic testing
• Risks of genetic testing
• Children

INTRODUCTION

Questions regarding whether or not to test at-risk children for Alpha-1 Antitrypsin Deficiency (Alpha-1) are escalating as a result of increased efforts to identify affected persons through targeted testing programs in the United States (1). These programs target at-risk individuals, including those who have otherwise unexplained liver disease or emphysematous lung disease. The impetus for increased testing is mounting evidence that early diagnosis and subsequent aggressive health management is effective to prevent or slow progression of Alpha-1 related disease (2,3).

Although some educational publications provide informed consent materials for the targeted detection programs, none is specifically geared to issues related to testing children or their role in the informed consent process. The purpose of this pilot study was to: (1) determine the information and role that parents and adults tested as children (ATC) want in the informed consent process; (2) describe the potential benefits and risks following from genetic testing of at-risk children for Alpha-1; (3) compare the views of parents and ATC with regard to testing at risk children and newborn screening. The goal is that this information will be pertinent both in recommendations and in fleshing out the risks and benefits included in the informed consent process prior to deciding whether or not at-risk children should undergo Alpha-1 testing.

BACKGROUND

The issue of genetic testing of at-risk children for late-onset diseases such as Alpha-1 is controversial because such testing requires that parents make decisions on their behalf (4). Currently, there is neither a practice standard regarding predispositional testing of children for adult onset conditions nor research addressing the informational needs of parents and children prior to genetic testing (1,5–7). Research into the needs of children with genetic conditions indicates that they want to participate in a more informed decision-making process and involve their parents as well (8–10). Some research regarding predictive genetic testing of children for adult onset conditions agrees with existing guidelines, other research argues that the guidelines are not justified (11–14).

Recommendations regarding genetic testing in children pivot on whether there is potential medical benefit following from testing. The question of whether children should be tested for Alpha-1 is explicitly addressed in the recommendations of the Alpha-1 Antitrypsin Task Force that call for restricting testing to at-risk individuals and children old enough to give assent (15). In addition, the American Academy of Pediatrics Committee on Bioethics states that, in the presence of clearly beneficial treatments or effective preventive strategies, genetic testing is justified when it is in the best interest of the child (6, 15–17). These recommendations call for explicit informed consent prior to testing from parents and assent from children over 7 years of age (18,19).

Such guidelines are traditionally based on the best interest standard and balancing clinical benefits and related risks (16). There is incontrovertible evidence of a direct cause and effect relationship between Alpha-1 related disease and environmental pollutants, e.g., smoking, second-hand smoke, dust, pollen, high levels of air pollution, cleaning solutions (20–23). The decision about smoking behavior is a very important one particularly for children testing as deficient or carrier status for Alpha-1 because smoking sometimes begins during adolescence, and it can affect their lung health. Therefore, early identification of Alpha-1 deficiency could alert parents and children to the undisputed need to avoid a host of environmental risks. Many may be amenable to taking steps to lower their exposures to these risks and subsequently reduce the possibility of developing Alpha-1 related disease in the future.

Empirical data about the psychosocial risks of genetic testing of children do not reveal serious harms (24). However, there are potential risks following from genetic testing of children. For example, there is some indication that young people may have heightened fears regarding education, future employment and eventual insurance discrimination (25–28). They will have to decide whether to disclose their test results to family members and others (15, 29–33). Many people may struggle with matters related to dating and entering into committed relationships (7,34). Others may grapple with reproductive decisions (7). Some may make lifestyle changes to reduce their risks in order to prevent or delay the onset of symptoms (25). Other potential risks of testing are: breech of autonomy and confidentiality (15, 19, 35–38); anxiety (39); impact on self and social image (34–40–44), negative effect on family dynamics (19, 29, 41, 45–47), delayed independence from parental figures (34), limited futures regarding higher education, employment, and reproduction (42, 45).

Recent studies suggest that parents and children do not indicate an adequate appreciation of benefits and risks of predictive genetic testing (14, 43). Moreover, the likelihood and magnitude of potential risks for persons tested is unknown. Given the uncertain status of federal oversight of the introduction of genetic tests into widespread clinical practice, the importance of information regarding the risks and benefits of testing and a robust informed consent process heightens. This pilot study explores attitudes toward testing at-risk children from the first hand perspective of those involved and describes the benefits and risks experienced therein.

MATERIALS AND METHODS

The project design included: (1) two focus groups in different parts of the country with parents who have made a decision about whether or not to test their children for Alpha-1 (parents), (2) two separate but similar surveys mailed to 228 parents and 131 ATC for Alpha-1 after excluding incorrect or duplicate addresses, (3) an expert advisory committee to assist with the formulation of recommendations for the informed consent process.

Focus groups with parents

The investigators conducted two focus groups with parents recruited from members of the Alpha-1 Research Registry from different parts of the country. To protect confidentiality, verbal consent was obtained from participants. The purpose of the focus groups was to inform the design, content, and language of the participant surveys. The focus groups used open-ended questions to explore the range of experience of parents with the process of informed consent prior to testing children, types of information provided prior to Alpha-1 testing, views regarding explicit informed consent for genetic testing, and the actual ethical and social risks and benefits following from the decision to test their children. The focus groups were recorded and analyzed for the range of responses, patterns and relationships of themes that emerged. The authors independently identified common themes from the qualitative data. The lists of potential themes were compared and differences resolved through critical reanalysis of the focus group narratives that resulted in additions, deletions, and modifications. The final themes that emerged from this iterative process determined question topics for the surveys.

Surveys of parents and ATC

The survey participants included parents and ATC from the Alpha-1 Registry and the ACT study. The purpose of the survey was to assess views of parents and ATC regarding informed consent practices prior to genetic testing of at-risk children (48). The survey assessed: (1) participants’ reason(s) for deciding to test or not to test their at-risk children for Alpha-1; (2) need for information about testing for Alpha-1 retrospectively, (3) experience concerning the benefits and harms of testing for Alpha-1.

Although most questions were identical, parents provided additional information regarding their family history of testing, and their assessment of most recently tested child's response. ATC provided first-hand information regarding specific impacts of testing. A draft survey was developed by the project team in the context of the results of the focus groups. The survey included multiple choice, Likert-type scale, and open ended questions. The final draft instrument underwent cognitive pilot testing among Registry participants (n = 10) using concurrent and post-completion discussion to identify and correct issues of clarity, order and format. The survey received IRB approval.

To protect confidentiality the research database identified members who met the inclusion criteria and provided permission for recontact, mailed the surveys, collected the data, and returned deidentified data to the study coordinator. An explanation of the study, its benefits and risks, the procedures in place to protect confidentiality, and the statement that return of the survey constitutes consent was included with each survey. The survey was coded and did not include any personal identifiers, rather it used alpha-numeric indicators for tracking of mailed and returned surveys. A self-addressed stamped envelope was included for returning the survey. Contact information on mailed surveys was maintained by the research database for a second and third mailing of surveys to non-responders. Because mailed surveys have the potential for a low return response, even those mailed to persons who have indicated willingness to be contacted about possible research participation, $1 was included in the first mailing to encourage return.

Data management

Survey data were entered in a secure, password-protected ACCESS database. The database was designed to mimic the survey forms and had range checks to aid in data integrity. Prior to analysis, data were reviewed for inconsistencies and possible outliers. Datasets were transferred to the statistician for analysis.

Statistical considerations

This study is primarily descriptive in nature, but in the planning stage we considered the statistical power available to detect differences between groups of respondents. Consider testing for differences in parent versus ATC responses. For a two-sided test of equality of proportions, with sample sizes 75 (parent) and 25 (ATC), and a level of significance of 0.05, we have sufficient power (0.80) to detect a difference of approximately 30% between the groups. For example, if the true population results are that 50% of parents would identify a reason for testing, but only 20% of ATC would note that reason, we would have an 80% chance of detecting this difference between groups.

Statistical analyses were performed using SAS, version 9.1 (SAS Institute, Inc, Cary NC) or R statistical software (The R Foundation). A p-value of less than 0.05 was considered statistically significant, with no adjustments made for multiple testing. Data from the surveys of parents and ATC were summarized using descriptive statistics and graphical methods. Chi-square tests (or Fisher Exact tests, for situations with small expected cell sizes) were used to compare parent and ATC responses. Tests of symmetry compared possible risks and benefits to experienced risks and benefits. Wilcoxon rank sum tests were used to compare age of responders to non-responders.

Expert advisory committee

An expert advisory committee convened with the research team for a 2-day meeting to examine the results of the study and to identify the ethical and social issues that emerged from the surveys, interviews, and focus groups and incorporate the data into the consideration of the normative principles of bioethics as well as the specific duties they generate.

RESULTS

Parent survey summary information

We mailed 228 parent surveys; 79 responses were returned (35% responding). Of the parent respondents, mothers filled out 86% and fathers 14%. The parent surveys requested information on all children considered for testing, a total of 164 children: 133 (81%) were tested and 29 (19%) were not. Parents provided further information on 26 of the 29 children not tested, indicating that 14 (54%) of the children would be tested in the future. For children tested, the current average age was 11.4 (s.d. 5.9) years; among those not tested, the current average age was 8.3 (s.d. 6.7) years. The remaining child-specific survey questions referred to the child most recently considered for testing.

ATC survey summary information

Of 131 ATC surveys mailed and not returned for incorrect address, 25 completed responses were returned (19% response rate). Of the surveys returned by ATC, there were 56% female and 44% male respondents. The current age of subjects ranged from 18–24 years of age; 75% of subjects reported that they had been tested between 15–17 years of age. Heterozygotes (PiMZ, PiMS) comprised 32% of the ATC and there were no homozygotes (PiZZ, PiSS) reported among ATC.

Reasons to test or not to test

Table 1 displays reasons identified as the top three reasons for testing. For both parents and ATC, the most frequently cited reason for testing was “at least one parent wanted to know child's status”. Other reasons cited frequently among the top three by both parent and ATC included “test results help planning for future”, and “at least one parent is a carrier.” Responses were similar for both groups, however ATC cited “parent recently diagnosed with Alpha-1” more frequently than parents. Two parents reported reasons for not testing their children that included possible insurance and employment discrimination, anxiety, and impact on future planning.

Table 1  Frequencies for each response identified as one of top three reasons for testing, and p-value comparing parent and ATC responses

	Parent (n = 79)	Adult tested as children (n = 25)	p-value
Parent wanted to know child's status	57  (72%)	22  (88%)	0.18
Test results help planning for future	43  (54%)	10  (40%)	0.30
Parent is a carrier	42  (53%)	11  (44%)	0.57
Parent found out about confidential testing	14  (18%)	4  (16%)	0.92
Child was symptomatic	12  (15%)	3  (12%)	0.94
Parent wanted earlier treatment for child	12  (15%)	1  (4%)	0.37
Parent recently diagnosed with Alpha-1	12  (15%)	10  (40%)	0.02
Parent wanted to help prevent child from smoking	10  (13%)	3  (12%)	0.79
Parent had worsening symptoms	5  (6%)	1  (4%)	0.95

Table 2  Listed below are frequencies and percentages in each category and p-value comparing parent and ATC

	Parent (n = 79)	Adult tested as child (n = 25)	p-value
When should child be tested? (multiple responses possible)
Under no circumstances	3  (4%)	0  (0%)	1.00
Prenatal screening	19  (24%)	4  (16%)	0.57
Child at risk, no symptoms, < age 8	48  (61%)	5  (20%)	0.001
Child is at risk, no symptoms, ≥ age 8	38  (48%)	10  (40%)	0.63
Child has symptoms	37  (47%)	2  (8%)	0.001
Don't know, no response	6  (8%)	4  (16%)	0.39
View of newborn screening programs			0.04
Very unfavorably	11  (14%)	1  (4%)
Somewhat unfavorably	6  (8%)	4  (16%)
No opinion	5  (6%)	7  (28%)
Somewhat favorably	25  (32%)	7  (28%)
Very favorably	30  (38%)	6  (24%)
No response	2  (3%)	0
How should children be involved in decision?			0.007
Tell child and ask permission	24  (30%)	15  (60%)
Tell child about test, don't ask permission	40  (51%)	6  (24%)
Don't tell child about test until older	9  (11%)	0
No opinion	7  (9%)	4  (16%)

Views regarding screening and testing of children

Responses regarding when children should undergo testing were varied, for both parents and ATC (Table 2). Three parents (4%) indicated children should be tested under no circumstances, but, in general, parents were more in favor of testing than ATC. Specifically, parents were more in favor of testing at-risk children with or without (and less than age 8) symptoms. Views of newborn screening also varied for both groups and differed between the groups. Parents hold more extreme views with 14% very unfavorable and 38% very favorable towards newborn screening, compared to 4% and 24%, respectively, for ATC. Opinions also differed between parents and ATC as to how children should be involved in testing. Although both groups indicated the need for child involvement, 60% of ATC respondents thought permission should be obtained, compared to 30% of parents.

Information and impact

Parents responded to questions as to what they were told prior to testing their at-risk child, and whether they had experienced these ramifications. ATC were asked to identify what information at risk children should be given prior to genetic testing for Alpha-1. Results are summarized in Tables 3 and 4. Information that parents received prior to testing varied; fewer parents reporting receiving information with potential negative impacts. A larger percentage of parents reported being informed of positive or factual information. Parents also reported experiencing positive impacts more so than negative. A large majority of ATC endorsed providing information to parents and children regarding access to insurance, inheritance and expression, impact on anxiety, association with smoking, and usefulness in planning for the future.

Benefits and risks of testing at-risk children for Alpha-1

Parents and ATC were asked to report the possible benefits and risks that they associated with testing at-risk children and those that they actually experienced, using a “never,” “rarely,” “often,” and “always” scale. These results are presented in Tables 5 (experienced and possible benefits) and Table 6 (experienced and possible downsides). For each component we compared the experience to the possible outcomes and also compared parent and ATC responses. For most benefits and risks, parents and ATC alike noted higher likelihood of possible risks and benefits compared to their actual experience. However, there were two categories where possible and experienced outcomes did not differ for both parents and ATC: the benefit “helps with planning for the future” and the risk “parents would experience anxiety.”

The experienced risks and benefits were similarly reported by parents and ATC, except the parents reported more benefits related to planning for the future than did ATC (p = 0.031). Possible risks were also viewed similarly by parents and ATC. Regarding possible benefits, parents felt more strongly than ATC that testing would lead to early treatment (p = 0.036), and that parents, relatives and friends may change smoking habits (p = 0.018).

Non-response comparisons

Demographic characteristics were available for those who did and did not return completed surveys. For ATC, groups did not differ significantly with regard to age, sex, race, or genotype. For parents, comparing those who responded to those who did not, no significant differences were detected for age, sex, or genotype. A larger proportion of the non-responders were non-Caucasian (7%) compared to responders (0%) (p = 0.012).

Expert advisory committee

From the resulting data and ethical analysis the expert advisory committee recommended that parents and children have relevant information regarding the risks and benefits of testing for Alpha-1 and that at risk children are directly involved in the decision-making process prior to testing.

Table 3  Listed are frequencies and percentages for parents’ responses regarding information and experience with testing their at-risk child

	What I was told when considering testing	What I personally experienced
Test results may affect access to health, life, and/or disability insurance.	38/74  (51%)	19/72  (12%)
Better understanding of family's genetics.	61/74  (82%)	66/74  (89%)
Genetic testing may entail an increase in anxiety.	35/75  (47%)	33/74  (45%)
Alpha-1 is a genetic condition that is associated with lung and/or liver disease	66/76  (87%)	——-
Alpha-1 testing should change cigarette smoking behavior	58/76  (76%)	——
Knowing my Alpha-1 results can help understand health risks and plan for the future.	66/75  (88%)	59/70  (84%)
Alpha-1 results may impact career choice or career opportunities.	33/74  (45%)	23/71  (32%)

Table 4  Listed are frequencies and percentages for ATC's responses regarding what children and parents should be told before testing

	What children from 8–18 years be told before testing	What parents should be told before testing
Test results may affect access to health, life, and/or disability insurance.	15/24  (62%)	20/24  (83%)
Better understanding of family's genetics.	20/24  (83%)	21/24  (88%)
Genetic testing may entail an increase in anxiety.	10/24  (42%)	20/24  (83%)
Alpha-1 is a genetic condition that is associated with lung and/or liver disease	22/24  (92%)	22/24  (92%)
Alpha-1 testing should change cigarette smoking behavior	23/24  (98%)	22/24  (92%)
Knowing my Alpha-1 results can help me understand health risks and plan for the future.	22/24  (92%)	23/24  (96%)
Alpha-1 results may impact career choice or career opportunities.	13/24  (54%)	20/24  (83%)

Table 5  Listed are row percentages in each category for experienced and possible benefits, comparisons of experienced vs. possible for each group, and comparison of experienced/possible benefits for parent vs. ATC

	Experienced benefit	Possible benefit	Experienced vs.
	N –R –O –A %	N –R –O –A %	Possible p-value
Leads to early treatment
Parent	31 4 24 40	0 0 31 69	<.001
ATC	54 8 17 21	8 0 40 52	0.038
Parent vs. ATC p-value	0.13	0.036
Child avoids smoking other environmental hazards
Parent	18 6 32 44	0 4 48 48	0.030
ATC	25 21 42 21	0 4 64 32	0.22
Parent vs. ATC p-value	0.15	0.39
Parents, relatives, friends change smoking habits
Parent	26 19 33 23	0 14 45 40	0.001
ATC	32 24 40 4	0 28 60 12	0.11
Parent vs. ATC p-value	0.18	0.018
Helps with planning for future
Parent	18 0 27 55	3 1 32 64	0.05
ATC	12 12 36 40	0 8 48 44	0.40
Parent vs. ATC p-value	0.031	0.11
Improve family relationships
Parent	34 21 32 14	8 27 39 26	<.001
ATC	29 38 29 4	12 32 44 12	0.29
Parent vs. ATC p-value	0.33	0.50

*Never –Rarely –Often –Always.

Table 6  Listed are row percentages in each category for experienced and possible downsides, comparisons of experienced vs. possible for each group, and comparison of experienced/possible risks for parent vs. ATC

	Experienced risk	Possible risk	Experienced vs.
	N –R –O –A %	N –R –O –A %	Possible p-value
Child experiences stigma/labeling
Parent	75 19 6 0	32 49 18 1	<.001
ATC	74 26 0 0	26 61 13 0	0.005
Parent vs. ATC p-value	0.60	0.76
Child experiences anxiety
Parent	49 43 8 0	17 53 27 3	<.001
ATC	48 35 17 0	9 61 30 0	0.029
Parent vs. ATC p-value	0.37	0.79
Child regrets testing
Parent	78 19 3 0	36 53 9 1	<.001
ATC	87 13 0 0	22 70 9 0	0.002
Parent vs. ATC p-value	0.74	0.53
Child blames parent for passing on alpha-1
Parent	77 19 4 0	24 53 21 1	<.001
ATC	65 26 9 0	22 43 30 4	0.030
Parent vs. ATC p-value	0.42	0.56
Child experiences negative impact on romantic relationships
Parent	81 19 0 0	35 58 4 1	<.001
ATC	74 17 9 0	30 57 13 0	0.019
Parent vs. ATC p-value	0.10	0.61
Problems getting health insurance for child
Parent	71 14 8 7	16 31 41 12	<.001
ATC	74 13 0 13	4 35 43 17	0.014
Parent vs. ATC p-value	0.52	0.52
Parents experience anxiety
Parent	34 21 27 18	17 21 44 17	0.09
ATC	39 17 35 9	4 35 48 13	0.23
Parent vs. ATC p-value	0.74	0.32
Test results worsen family relationships
Parent	79 18 1 1	47 47 5 1	<.001
ATC	83 17 0 0	39 57 4 0	0.012
Parent vs. ATC p-value	1.00	0.84

*Never –Rarely –Often –Always.

DISCUSSION

This methodology of surveying ATC and parents proved to be an appropriate way to put some substance to the discussion of potential risks and benefits of testing children for Alpha-1. Currently, informed consents for Alpha-1 merely state the possibility of certain benefits and risks but do not offer any indication of the frequency or degree of benefit and risk. As a parent considering testing your child for Alpha-1, it is of limited value to know that employment discrimination might occur, or that testing might affect future personal relationships, without knowing the likelihood of those risks, and if those risks are usually harmful or just minor annoyances.

The advantages of this methodological approach are that it offers some insight into the risks and benefits as perceived by those tested. It also offers the advantage of a perspective that often is several years removed from the test event, giving the persons tested and the parents that tested their children time to assess the severity of the risks and benefits. This is important since many of the theoretical potential risks and benefits will not be likely revealed until several years after the testing and diagnosis of Alpha-1. One downside of this methodological approach is the risk of recall bias. Parents and ATC might not accurately recall the reasons for testing or remember the discussion of potential risks and benefits at the time of testing. However much of the survey was not subject to recall bias as it queried the subjects about their current experiences and feelings regarding genetic testing.

Further research using this methodology should use larger subject population and ask additional direct questions about frequency of benefits and risks plus details of the benefits and risks experienced. Additionally, the preliminary focus groups convened in our pilot study indicate that, although time consuming, in-depth interviews with this subject population should reveal important additional data concerning the severity of the associated risks and the degree to which those tested benefited.

Our pilot study indicates that the possible risks as reported by the participants following testing for Alpha-1 are overblown. Interestingly, the possible benefits are likewise exaggerated. Respondents expressed significantly higher expectations of possible risks and benefits following Alpha-1 testing than they actually experienced. This study confirms what other recent studies report for other genetic diseases: significant risks reported by those being tested and by their parents are rare (24). This may indicate, if confirmed by follow-up studies, that current informed consent information is not adequately understood.

It may be the case that when risks and benefits are just broadly identified, without including information about the frequency or seriousness of the possible risks and benefits, that subjects tend to magnify and understand these risks and benefits in terms of worst care or best case possibilities. This may lead to an inaccurate view of the actual risks and benefits, and it is not known if this in actuality would cause some to refuse testing or some to seek testing. It may also indicate that in the absence of firm and clearly presented data about the frequency and significance of risks and benefits parents may over estimate the possible risks and benefits thus making a decision on inaccurate perceptions.

One argument is that testing for Alpha-1 and other rare genetic diseases is frequently regarded as a routine medical test that requires no specific or detailed informed consent process or information prior to the delivery of test results. However, according to our pilot data respondents highly supported providing information regarding access to insurance, inheritance and expression, impact on anxiety, association with smoking, and usefulness in planning for the future to parents and ATC prior to testing for Alpha-1.

This study begins to answer the question of what people want to know in the informed consent process prior to testing. The danger implied by this finding is that parents may expect too much from the test and also they may worry too much about risks which are unlikely to occur. It is not clear from our pilot study whether a more robust informed consent process will give parents a more accurate view of both the risks and benefits of testing. Parents tended to recall positive and factual information provided prior to testing, however negative information (e.g., increase in anxiety) may have been provided but not remembered.

Somewhat surprisingly, our pilot study showed significant differences between the views of ATC and parents. When testing at risk children, more ATC thought that the child should be asked for permission prior to testing than parents. Although identifying and analyzing these differences was not a primary goal of the study, it does indicate a significant difference that should be explored in future studies. These results reflect ATCs views as adults retrospectively. It would be interesting to see if adolescents feel this even more strongly than our responses from ATC. At any rate,one important finding from our pilot study is that ATC report that they would wish to be informed of the testing decision and involved in the decision making process, including being informed of the potential risks and benefits of testing.

These data replicate other studies reporting the role that children want to play decision-making process prior to testing (8–10). Furthermore, no significant harm was reported by those tested as children as a result of knowledge of being tested for Alpha-1. If this is borne out by future studies it clearly indicates that the doctrine of assent should be applied to genetic testing of children, and this may be powerful evidence for future policy recommendations for genetic testing of children. Additionally, this evidence would also be important for parents who are considering whether to inform or involve their children in the testing decision.

Another controversial area for genetic testing is whether testing for late onset genetic diseases, which have no time sensitive and effective treatments, should become part of the regular newborn screening panel of tests. Many in the Alpha-1 community have advocated for newborn screening given that life style changes may make a significant difference in the onset and severity of symptoms. With Alpha 1 the current major interventions are more closely monitoring and avoiding environmental pollutants, including tobacco smoke for which evidence suggests will reduce the onset and seriousness of Alpha 1 symptoms. Although there were significant differences between the groups, a majority of both groups were in favor of newborn screening.

We do not know the reasons for the objections to newborn screening, and this is an area for further research (49). If this evidence that newborn screening would be acceptable to and desired by the affected populations is borne out by future studies it could serve to promote genetic screening for this and other late onset genetic diseases. This would be true especially if testing costs continue to decline and if relative risks that have been broadly identified prove to not be likely or serious or can be mitigated by public policy.

As our pool of subjects in this pilot study was limited, the population sampled may not be an accurate representation of the breadth of experience of parents with at-risk children or ATC in general. Due to the low response rate, caution should be used when generalizing the results. We had anticipated a higher response rate, but this is a difficult target population to identify, the survey was complex and we did not have alternative formats (phone, internet) by design, and we did not have direct contact information for potential subjects. However, we were able to detect differences between parents and ATC that were intriguing, and demonstrate that the expectation of possible risks and benefits exceeded those experienced. Further investigation into the effects of testing for Alpha-1, with more in-depth interviews and a larger population sample is needed to refine and or confirm the results of this pilot study.

CONCLUSION

The results of this study suggest that parents and ATC want to be involved in testing decisions and expect to be told of the risks and benefits of genetic testing for Alpha-1. Although these data replicate research into the needs of children with other genetic conditions and appear to be in line with current ethical and legal thought about informed consent, this is not the currently agreed upon practice. In addition, both groups studied expressed a need for more information about the actual risks and benefits and the frequency and significance of both the risks and benefits of testing for Alpha-1. The results of this pilot study do not reveal serious harms from testing at-risk children, but currently hard data on the risks and benefits simply does not exist. In the absence of multi-year longitudinal studies of these risks and benefits, ATC are a promising population to reveal crucial information for an ethically appropriate consent process.

Our pilot study also confirms that further study involving ATC will be useful in the future decisions about whether to include late onset genetic diseases in newborn screening programs. Parents and ATC differed significantly with regard to their views on newborn screening and how children should be involved in the decision making process prior to testing. ATC were moderate in their views about NBS, while parents held more extreme views, both positive and negative. Our data do not show if these reactions are opinions about the risks and benefits of newborn screening or if these views are based on their actual experiences following from a childhood test for Alpha-1. Before late onset genetic diseases such as Alpha-1 are included in newborn screening panels these research questions should be further explored.