Concerns of Newborn Blood Screening Advisory Committee Members Regarding Storage and Use of Residual Newborn Screening Blood Spots

Abstract

Objectives. We assessed attitudes and opinions of members of newborn blood screening (NBS) advisory committees regarding the storage and secondary research use of residual specimens from NBS.

Methods. We conducted focus groups in 2008 and 2009 with NBS advisory committees (4 focus groups; n = 39 participants) in the Mountain States region (i.e., AZ, CO, MT, NM, NV, TX, UT, and WY).

Results. Participants identified several challenges to implementing policies for storage of and research on residual newborn blood specimens. Themes that emerged from the data were public health relevancy; improvement of parental knowledge; impact of enhanced parental involvement; concerns over ownership, privacy, and confidentiality; identification of secondary research uses; and role of advisory committees.

Conclusions. Participants indicated that secondary uses of residual specimens entailed opportunities for improvements in NBS programs but also carried significant risks for their programs. Addressing concerns from stakeholders will be necessary for state-level adoption of national recommendations.

The operation of newborn blood screening (NBS) programs is a core state public health service.¹ These programs collectively represent the largest application of genetic testing in the United States.² NBS is critical for preventing significant morbidity and mortality by screening almost every baby born in the United States within the first few days of life. Blood obtained from a heel stick is dried on filter paper to conduct testing for several conditions. States vary somewhat in testing procedures and conditions targeted.

Cumulatively, state health departments receive dried blood spots (DBSs) on filter paper from approximately 4 million newborns per year. At the time of the heel stick, more blood is drawn than may be necessary to complete the NBS tests, to ensure that there is sufficient blood available if reanalysis is needed, and to facilitate quality assurance protocols. Consequently, if residual newborn DBSs were accumulated over time, almost the entire population of children born in the United States would be represented. The length of storage and secondary research use of DBSs differ significantly by state and are of major concern within the state NBS programs.³

Residual DBSs historically have been used for quality control and evaluation of new tests in NBS programs. Quality assurance applications of residual samples have not been controversial and are often considered authorized as an integral component of NBS programs. Residual DBSs have been increasingly recognized as a valuable source for other biomedical research uses outside the scope of the NBS. For example, residual DBSs have been used for infectious disease epidemiology, genetic epidemiology, environmental agent epidemiology, birth defects studies, and population-based studies.^4–7 However, the potential use of residual DBSs for biomedical research unrelated to NBS has raised several ethical, legal, and social dilemmas among ethicists, public health officials, policymakers, and researchers.^7,8

At the national level, the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children is developing policy recommendations for storage and secondary research use of DBSs.⁹ The American College of Medical Genetics also has released a position statement on the importance of DBSs for biomedical research.¹⁰ The development of state public health policy, however, occurs at the state level. Accordingly, state-specific concerns should be addressed at the state level.

Policy developments at the state level have historically used advisory committees to provide input, direction, and representativeness of various stakeholders and the public.^11–14 In 2000, an American Academy of Pediatrics task force developed a report to address policy concerns raised by state NBS programs.¹¹ The report included a recommendation that advisory committees should be established in each state to provide guidance on policy developments in NBS programs.¹¹ Involvement of advisory committees with policy developments was also recommended previously by the National Institutes of Health Task Force on Genetic Testing for Promoting Safe and Effective Genetic Testing in the United States.¹² The Council of Regional Genetic Networks similarly recognized and valued the role of advisory committees and recommended that each state have at least 1 advisory committee that included health care professionals, families, and the public.¹³

Recent lawsuits in Texas and Minnesota over the storage and secondary use of DBSs have increased scrutiny of how DBSs are managed and of the roles advisory committees might play regarding this important issue.^15,16 Because no research has been conducted on how advisory committees view this policy issue, we convened focus groups with state NBS advisory committee members to ascertain attitudes and opinions regarding the storage and secondary research use of DBSs. This research was a component of a larger project aimed at promoting public dialogue on the use of residual NBS samples for research funded by the National Human Genome Research Institute.

METHODS

We chose to conduct our research with NBS advisory committees in the Mountain States region of the United States (i.e., AZ, CO, MT, NM, NV, TX, UT, and WY), 1 of 7 regional Genetic Service and Newborn Screening Regional Collaborative Groups established by the Maternal and Child Health Bureau of the Health Resources and Services Administration. The regional collaboratives were established to address the rapidly expanding and changing role of NBS and the challenges associated with these changes, such as geographic maldistribution of genetic specialist and subspecialist expertise.¹⁷

An NBS status report indicated that all but 2 states were required to have or did have NBS advisory committees.¹⁸ We narrowed our focus to the Mountain States region collaborative because it contained a manageable number of programs for the methods of our study, and the NBS status report indicated that all states in this region had established advisory committees.¹⁸ All 8 of the states in the Mountain States region were invited to participate, but only 4 states had active advisory committees at the time of our research. Our agreement with these committees before beginning data collection was that our project would not identify responses by state.

Focus Groups

Our 4 focus groups (n = 39) comprised members of 4 individual state advisory committees. The meetings took place between November 2008 and June 2009 and lasted between 1 and 2 hours. The professional characteristics of the participants are shown in Table 1.

TABLE 1.

Professional Characteristics of Newborn Screening Advisory Committee Members in Focus Groups Discussing Storage and Use of Residual Newborn Screening Blood Spots: US Mountain States Region, 2008–2009

Characteristics	Group 1, No.	Group 2, No.	Group 3, No.	Group 4, No.	Total, No.
Medical directors	2		1		3
Lab directors		1	1		2
Cystic fibrosis specialty clinic personnel (MDs and RNs)		2
Sickle cell specialty clinic personnel (MDs and RNs)				2	4
NBS staff (coordinators, managers, hearing screening)	5		5	3	13
Community members (parent of affected child)	1	1	1		3
Genetic counselors	2			1	3
Metabolic dieticians		1			1
Pediatricians	1	1		2	4
Local nonprofit community directors		1	1		2
Geneticists		1	1		2
Metabolic subspecialists (MDs)		1			1
IRB analysts			1		1
Total	11	9	11	8	39

Note. IRB = institutional review board; MD = medical doctor; NBS = newborn blood screening; RN = registered nurse. Mountain States region consists of AZ, CO, MT, NM, NV, TX, UT and WY.

A professional transcriptionist recorded and transcribed the proceedings of the focus groups. A member of the research team (ER) verified all transcription work. The focus group format followed recommendations by Krueger and Casey regarding preparation, engaging participants, and moderating the discussion.¹⁹ Before beginning the sessions, we provided an overview of the research project to participants. We moderated the groups according to a semistructured interview guide developed from expert opinions and published literature. We asked participants to give their opinions as representatives of the advisory committee, and we probed for clarification of their responses and further details.

We designed the questions to evoke conversation, use words the participants would use when talking about these issues, be concise and open ended, and follow a logical questioning route.¹⁹ The questions were:

• What are your opinions on the storage of residual newborn samples for research use?

• What role do you think parents should play in the storage and use of residual newborn samples?

• What role do you think the public should play in how these samples are governed?

• What role do you see education playing in regard to the storage and use of residual newborn samples?

• What do you think are some acceptable and unacceptable research uses for the residual samples?

• What should be the role of the advisory committee in regard to the storage and use of residual newborn samples for research?

Data Analysis

We conducted a qualitative content analysis of the data from the focus groups. A distinguishing feature of content analytic approaches is the use of a consistent set of codes to designate data segments that contain similar material. We generated the codes by careful reading and analysis of the transcripts rather than through automated search algorithms. After we compiled the template for coding, we systematically applied it to the data, adding additional codes as needed to capture categories that were missed initially.²⁰

After coding was complete, we summarized the codes and recontextualized the data to identify patterns. During this process, we continuously compared data among the groups.²¹ Further examination of the data to explain why patterns occurred was a significant component to the data analysis because it allowed a contextual and interpretative understanding of the phenomenon.^22,23

We used ATLAS.ti version 6.2 (ATLAS.ti Scientific Software Development GmbH, Berlin, Germany) to help analyze the data and to maintain an audit trail. The box on page 2113 provides an overview of the results.

Concerns of Newborn Screening Advisory Committee Members Regarding the Storage and Research Use of Residual Newborn Screening Blood Spots: US Mountain States Region, 2008–2009

Issue	Concern
Public health relevancy	• Relation between storage and use of DBSs and the purpose of NBS and public health
	• Limited resources constraining health departments
Lack of parental awareness about NBS	• Need to improve education about newborn screening
	• Educating parents about the retention and use of DBSs might reduce current NBS participation
Impact and extent of parental involvement	• Parental consent for storage and secondary research use of DBSs
	• Informed consent might interfere with current NBS participation
	• Ability of new parents to fully appreciate the consent process
Privacy/confidentiality	• Discrimination
	• Anonymity
	• Increasing transparency and building trust with parents
Secondary uses of samples	• Beneficiaries
	• Obligation to inform donors or their parents
Ownership of samples	• Unclear whether donors or the government owns the sample
	• What happens if stored until donor is aged 18 years
Role of NBS advisory committees	• Some type of advisory committee needed to govern access to samples
	• Few nonmedical professionals on current committees

Note. DBS = dried blood spot; NBS = newborn blood screening. Mountain States region consists of AZ, CO, MT, NM, NV, TX, UT, and WY.

RESULTS

Overall, participants thought that secondary uses of residual specimens offered opportunities for improvements in NBS programs. However, some participants were unsure about the relationship between storage and secondary research use of DBSs to the public health mission of NBS programs. Participants questioned whether it was within their institutional responsibilities to store DBSs beyond the time necessary for NBS. As one person put it,

And there's also the [question], “Why do you have me run screening; is it to do research, or was it because you wanted to screen for whatever disorder a child might have and help that child in that family?”

Some participants felt that identifying the secondary research purposes ahead of time and how that research related to improving the health of the public would help establish a positive relationship between the NBS program and storage of and research with DBSs. For example, participants commented that “I think it depends in part on the type of research that you're doing,” and “I can see using the samples for sort of public health, seeing as they're part of the public health system already.”

Lack of Parental Knowledge About Newborn Screening

Another challenge that participants identified for policy development for secondary use of DBSs was that not all parents are adequately informed of their state's NBS program. Although brochures were the most common method for informing parents about the program, participants were unsure whether and when the parents read them. In addition, the birth of a child is a hectic time, and even if parents are informed, they might not be attentive to such information. To develop policies governing the storage and research use of DBSs, many participants felt that parents first must be adequately informed about the NBS program. Suggestions to improve parental knowledge about NBS included providing education during the prenatal period and informing them through mass media such as newspaper, radio ads, or commercials. Overall, participants recognized that education about NBS would be challenging but necessary. Participant comments that exemplified these concerns included these:

It's a thorny issue because I think all of us around the table know that the current process of understanding the newborn screening as a program is hardly sufficient. I don't think there is any [one] of us [who] would say that most parents, when they have their new baby, understand exactly what's going on as part of the newborn screening processes.

People don't even know that newborn screening happens, and I know after having children, when you get stacks this high before you walk out the door, nobody reads it, so there's got to be a different mechanism.

Impact and Extent of Parental Involvement

Another primary concern of participants was the changing role of parents in NBS and how it would affect current participation. Concerns about decreased participation in NBS stemmed from the potential for adverse impacts from increased education regarding research on DBSs. If parents did not want their child's DBSs to be used for research, they might not undergo NBS itself. The following comments illustrate the feelings on this issue:

I agree that there are important reasons for storing [DBSs]; my concern is, will that encourage some of them [parents] to opt out of newborn screening itself?

We're already seeing issues in states where people are trying to opt out of newborn screening and, because it's so difficult to explain all this, and we can all see the obvious beneficial implications of the research. You open this up and then suddenly people are like, okay, I don't even know that I want to have a newborn screening done.

Most of the participants also indicated that parents should be asked for their consent for storage and secondary research use of DBSs and precautions should be taken to prevent adverse consequences from NBS. Comments included “How you get consent is going to be very problematic because it could interfere with people consenting to the test,” and “It is the parent's choice whether that sample then is destroyed after the newborn screen or is stored for future use. But it brings it back to the parent to make the decision to store that sample.” No consensus emerged on a best approach for seeking consent (opt in vs opt out), but participants acknowledged that the logistics of implementing such a process would be complex.

In addition, we heard concerns about how to assess parental understanding of the consent process, such as

Really what is informed consent? You sign a piece of paper, you sign your informed consent, something comes back later on, and [you] say, ‘Well, I didn't really understand that; that really was not exactly what I was informed of.’ Informed consent is a very difficult process regarding newborn screening and DNA testing.

Privacy and Confidentiality Concerns

Participants mentioned that privacy and confidentiality would be significant concerns because research on DBSs could potentially drive discrimination by insurers and employers (“I would think the crux of the issue would be also maintaining privacy and assuring there isn't going to be any kind of discrimination for the person if something is found out as a result of that genetic test”). Others were concerned about the safeguards for ensuring anonymity (“There is more access to our health information than there has ever been, and they're sharing even with insurance companies, and I really am concerned until such time as there is some kind of protection”). In addition, participants pointed out that a small segment of the population was distrustful toward government entities and would not feel comfortable with storage and secondary research use of DBSs even if safeguards were in place to protect individuals. As one participant commented,

there really is consumer fear out there. I mean, within the last month or 2, I've had a call from a parent who refused newborn screening because they assume that there is a national database.

Secondary Uses of Samples

Several participants said that parents should be informed before the screening about the type of research that would use DBSs. However, the complexities of identifying future research with DBSs would be problematic because of the ever-changing nature of genetic and technological advancements. Some participants felt it would be necessary to identify whom or what the research would benefit, such as public health, children, or a specific disease or treatment. Outlining the secondary research uses of DBSs should also address whether research will be conducted with anonymous or identified samples.

Interestingly, participants had mixed opinions on the benefits of anonymous or identified DBSs for research, but most participants discussed concerns parents might have if a child were diagnosed with a specific disease or condition and the importance of communicating this information to them. These concerns included: “There may be something next year that comes up and says, ‘This is an amazing test that will benefit X, Y, or Z.’ … Genetics is changing so fast, and it may not even be just genetics”; and “What do you do with the information? If it's de-identified, do you re-identify it and contact the families? What do you do with that?”

Ownership of Samples

Another issue identified by participants was ownership of residual samples. Some participants felt that the state owned the samples; others, the parents; and some were unsure (“Whether it's the family, whether it's the health department or whether it's the state … who owns the samples?”; “I think I would come to the decision [that] the family probably owns them. Let me put it this way: the precedent here is that the health department won't release the sample to us for 1 reason or the other without the family's permission”).

Participants also discussed transfer of ownership of DBSs in the event they were stored for a considerable period. Participants noted that policy developments may also need to address what happens when a donor turns 18 years of age: should consent be obtained from the donor or does consent by the parents automatically transfer to the donor (“These people are going to grow up, and in 20 years it's going to be their own personal DNA”)?

Role of Advisory Committees

Participants were asked about the role the NBS advisory committee should play in developing policies for storage and secondary research use of DBSs. They noted that the committee was primarily advisory and would not have the authority to make decisions regarding DBSs. However, some type of advisory committee would be needed to provide oversight for access to the samples (“Like some type of an oversight to it. Nobody can just have access; there's got to be some type of an oversight to it like we have in an advisory committee”; “We would be recommending what the system should look like to whomever has the final say of approval”).

We noted differing views regarding whom the advisory committees represented. Some participants felt they represented the community or at least understood the concerns of the community, and others disagreed. The most common opinion was that the committees represented medical experts in the community (“I would say we represent the medical community, we haven't always had great luck with getting consumers involved in our advisory committee”). Participants supported involvement by parents with and without affected children as a necessary component of NBC advisory committees (“[What we need are] parents on the advisory committee. If you're going to have an advisory committee that releases samples for research, you should have parents”).

Participants were unsure, however, about public representation—how the public should be defined and whether an advisory committee would be representative of the public. When asked about the role of national guidance, participants said guidelines would be helpful, but they were also unsure about how such guidelines would be implemented at the state level (“The national legislation is usually much broader. And then it comes down to the state, and the state takes it and will adapt it to fit their state's needs”).

DISCUSSION

Our research, which was part of a larger study, aimed to evaluate the views of members of NBS advisory committees regarding the retention and use of DBSs. Advisory committees have been an important part of policy developments for public health programs. In addition to providing scientific guidance on genetic testing, they are essential for identifying ethical, legal, and public policy concerns regarding advancements that involve human genetics, such as the storage and research use of residual DBSs.²⁴ The value of advisory committees to NBS programs was also reinforced by the American Academy of Pediatrics–Health Resources and Services Administration Newborn Screening Task Force, which strongly encouraged development of advisory bodies that comprised a range of individuals, from health care personnel to community members, to provide diverse perspectives.¹¹

Our study was among the first to document concerns of advisory committees regarding policies for the storage and use of residual DBSs. Our results raise more questions than answers but should encourage further research to determine whether these attitudes are consistent among other state advisory committees. In addition, our findings provide preliminary suggestions for developing policies for the storage and use of residual DBSs.

Participants identified ethical issues that will affect policy development for the retention and use of DBSs. They were concerned that the retention and use of DBSs could jeopardize the public health mission of state NBS programs on 2 levels. First, they noted the current lack of knowledge among parents about existing NBS programs and feared that educating parents about the retention of DBSs for secondary research use could lead to increased refusal rates for NBS. Second, some participants questioned whether the primary purpose of blood collection was to screen babies or to accumulate research samples. The concern that the retention and use of DBSs could undermine the integrity of NBS programs is crucial. This concern highlights the need for greater transparency in the policy development process and the need to educate parents further about NBS in general and possible future research with retained samples.

Increasing transparency and trust have been discussed as significant concerns for the application of genetic and technological advancements in the public health field.^25,26 Increasing transparency through education among communities, researchers, and government agencies can create a climate of openness and may enhance application of genetic and technological advancements in the public health domain.²⁶ Additional concerns about privacy and confidentiality of information identified in our focus groups underscore the need to develop robust privacy protections. Specific information about these privacy protections should be communicated to parents and the general public to help foster trust in the research enterprise and build support for the retention and use of DBSs.

Participant comments also reflected the need to clarify the role of parents in the decision-making process. Each state will need to develop a mechanism by which parents are informed about the retention and potential use of DBSs and decide what level of parental involvement is appropriate. Similarly, the question of which party retains ownership of the residual sample should be clarified. The answer to this question has significant implications regarding what say, if any, parents may have in the decision-making process.

Finally, participants recognized the value of advisory committee recommendations to state policymakers regarding the retention and use of DBSs. They noted the need for greater involvement from community members, particularly parents, in the policymaking process. The advisory committees in our study were primarily composed of medical and health department employees, with approximately 1 parent per group with a child diagnosed through the NBS program. Previous research found minimal involvement of consumers at all levels of state NBS programs.¹⁴ As state legislatures and public health departments grapple with these issues, the membership of NBS advisory committees should be considered carefully, and increased participation by members of the lay public should be encouraged. These advisory committees provide a mechanism by which a broad range of community perspectives may be obtained.

Advances in genetics and technology have increased opportunities and demand for biomedical research using DBSs.²⁷ However, some authors have argued that genetic and technological advances have grown faster than have the state health department readiness and capacity to sufficiently address the practical and ethical challenges associated with this increased demand.^7,28 Participants in the focus groups recognized that this area is a complicated one and that policymakers face numerous challenges. Research is needed to assess the impact of the changing roles of NBS on public attitudes and participation in the screening programs. In addition, national recommendations may need to take into account the attitudes and opinions of advisory committees. Seeking input from a variety of sources is essential for ensuring that the ethical implications of storage and secondary use of DBSs are properly addressed.