Working Paper #95-4(1)
By Angie Jeffords
Department of Sociology
University of Colorado, Boulder
This paper was written with a small grant from the Conflict Resolution Consortium, University of Colorado. Funding for the Consortium and its Small Grants Program was provided by the William and Flora Hewlett Foundation. The statements and ideas presented in this paper are those of the author and do not necessarily represent the views of the Conflict Resolution Consortium, the University of Colorado, or the William and Flora Hewlett Foundation. For more information, contact the Conflict Resolution Consortium, Campus Box 327, University of Colorado, Boulder, Colorado 80309-0327. Phone: (303) 492-1635, e-mail: crc@cubldr.colorado.edu.
Copyright (C) 1995. Angie Jeffords. Do not reprint without permission.
1. INTRODUCTION
It is now possible for the medical world to identify many of our most mysterious and darkest biological secrets. The ability to screen DNA for defects and manipulate genetic material through gene therapy have opened a "Pandora's box" of questions and controversy regarding reproduction, psychological and social stigmatization, and the preservation of life. Once the secrets of our genetic makeup are discovered, what is done with the information becomes a whole new set of potential conflicts. Who has the right to this information and what can or should be done with it? This question creates ethical and religious debate at many different levels. Infant screening for the genetic condition of Cystic Fibrosis (CF) is plagued by this type of controversy. Presented here is an analysis of that controversy and a possible solution to help resolve it.
The controversy surrounding the newborn screening for CF is complex and finds itself in many different arenas affecting moral, ethical, religious, and political debate. There are also many parties involved in these issues: those in various medical communities, families who have a child with CF and the families who test false positive for CF, friends and communities whose membership includes individuals who have CF, law makers, insurance providers, ethicists, and those who are both for and against "family planning." Until recently, children with CF did not live into adulthood so they were a population without a direct voice in the matter. This too has had its influence over the debate, as they begin to speak out for their own needs and interests. This list can easily expand to all of society.
Cystic fibrosis is the number one genetic killer in the Caucasian population; one person in every 20 is a carrier of this autosomal recessive gene. One in every 2000 individuals has CF. CF is most commonly characterized in two major ways, the pancreas and the lungs. A thick sticky mucus is found in these two organs, and it is that mucus that causes all the trouble. The thick mucus blocks the natural enzymes in the pancreas from doing their part in the digestive process, which directly affects the growth and nutritional well being of a person with CF. By taking enzyme replacements in addition to extra vitamins, the condition can be managed quite well, and with today's enzymes a patient can grow normally. The condition in the lungs is not so easily normalized. The mucus builds up in the airways and eventually leads to chronic lung disease and consequently premature death.
In the late 1970's, discussion began to grow surrounding the possibility of screening for CF. The development of new methods for newborn screening throughout the next decade increased the potential for an effective screening program. In 1989, the gene for CF was isolated, which not only gave fuel to the discussion surrounding the costs and benefits of screening, but also fire to the debate. Much of this debate exists within the medical world itself. Is there a benefit for the patient by being identified through the newborn screen? To make this determination, what kind of study, if any, should take place? If a screening does take place, what method should be used? And, if we do screen with a DNA determination, what are the implications and is that an area that should even be addressed at the newborn stage?
With the isolation of the gene, it will also now be possible to work towards forms of gene therapy and eventually a cure. Finally the outlook for people with CF is optimistic, and children can begin to plan a future. However, there may continue to be discussions within the medical community along with political and policy making bodies as how best to carry out these new treatments and when a cure can be called a cure and then used as one.
Should there be a newborn screening for CF in all infants? It would appear that most all concerned with this question agree that the answer is found by evaluating the costs and benefits of conducting such a wide-spread screening. People want to know that there is a direct benefit to those diagnosed at birth with CF as opposed to waiting until the condition manifests itself clinically. The way one interprets "direct benefit" is cause for much debate. Once one determines direct benefit, then those benefits must be weighed against the costs involved. Many of these costs and benefits go far beyond the child. The following is a list of some of the primary costs and benefits involved in this issue:
In 1964, the first newborn screening method was developed for screening newborns for the genetic condition of Phenyketonuria (PKU). This method was identified by Dr. Robert Gutherie. Dr. Gutherie faced much controversy over his intention to screen all newborns by means of the PKU dried blood test. At that time people were fearful of "Socialized Medicine." Dr. Gutherie eventually succeeded with the implementation of the PKU screen, and the testing was implemented in all 50 states. This legislation was made possible only with the help of parents and PKU advocates.
In 1973, an immunoreactive trypsin test (IRT) was developed that could detect CF in newborns. This test requires that blood be drawn within the first few days of life and could be "piggy backed" on the blood drawn for other newborn screening. If the first IRT comes back positive, then a second blood draw is done in the third or fourth week of life. If the results of that IRT screen are also elevated, then a sweat test is conducted offering families a final diagnosis. This diagnosis can be achieved as early as the first month of life. This method of screening is identified as a two-tiered IRT sweat test.
This test produces a high number of false positive results, 93 percent on the first draw and 60 percent on the second. The sweat test is highly conclusive, and in either case (positive or false positive), it is the determining factor for diagnosis of CF. This test also has the ability to diagnose true positive for CF at about 97 percent, including cases of meconium ileus and 88 percent without. This test is relatively inexpensive, at approximately $1.50 per baby. There are an estimated 50,000 children born in Colorado a year. The first IRT is done on the same blood draw as other newborn screenings; therefore, it is not necessary to use an extra draw. The laboratory process is also much more routine for the IRT than the DNA test and does not require special training.
The IRT DNA test is extremely accurate in the diagnosis of the most common CF genotypes, but it is expensive and requires more skilled laboratory work. The false positive rate is very low; however, not all genotypes can be tested (there are over 100 known genotypes). An infant with a less common genotype would not be identified. However, because there are so many possible genotypes for CF, it is not efficient to screen for all of them in a state-wide screening program of all infants; therefore, it is possible that the less common unscreened genotypes would not be diagnosed by the screening program. The DNA screening will identify carriers of the CF genotypes that are screened for in the program. This may potentially subject babies to psychological and social stigmatization. It also may lead to suffering due to the many misconceptions surrounding CF. One of the ethical concerns in using the IRT-DNA test is that by identifying this specific genotype of the infant parents can be prompted to be tested themselves which could lead to a definitive identification of the biological parents. This could disrupt the family if the father is not identified as the biological parent. Another serious repercussion of the DNA tests is that identification of carriers might be an influence over individuals when choosing a partner.
How a given state prioritizes the costs and benefits of newborn screening for CF will determine how they will proceed in choosing to implement a screening program. This process of decision making in the medical world has been the source of a long-standing debate. Should a long-term controlled study be conducted to determine accurately the outcome, in this case, of a screening program? Or should the program begin immediately with the support of existing information and hypotheses? In the discussion over the implementation of a state-wide screening for CF, there have been two states who have exemplified this process well, Colorado and Wisconsin.
On June 20, 1987, the Colorado State Legislature passed an Act that provided funding for newborn screening programs across the state. That funding was for over $250,000. This included the screening for CF. In their words, "The general assembly hereby funds, determines, and declares that this act is necessary for the immediate preservation of the public peace, health, and safety." This program was brought to Colorado law makers by the medical community in addition to Colorado families. It was believed that there was sufficient evidence of both long- and short-term benefits to the infant and their families to push for the immediate implementation of the screening program for CF. Along with the decision in Colorado to screen came the determination to use the two-tiered IRT and sweat test. This test has continued to be supported over the IRT-DNA method. There is a great deal of debate within the medical community and beyond regarding the costs and benefits involved with each of the two screening methods, the IRT and the IRT DNA.
Colorado has seen success in the implementation of their screening program. They have had the opportunity to look closely at children with CF from early on in life and evaluate their progress and immediate needs. It has also allowed for more research opportunities at a much younger age and in greater numbers in their first year. While additional research needs to occur, it appears the initial hypothesis (that screening is overall beneficial) can be supported.
In 1983, a task force was convinced by the Cystic Fibrosis Foundation to review the complex and controversial issues surrounding the costs and benefits of a state-wide newborn screening program. It was the determination of this committee that further research and analysis must first be done before a definitive decision could be made. The CF Foundation supported Wisconsin in its pursuit of evidence, which could tip the scales one way or the other on screening issues. "The purpose of adding this new test on a research basis was (1) to determine the pulmonary and nutritional early diagnosis, (2) to establish the efficacy of the IRT assay as a screening test, and (3) to evaluate potential adverse psychological consequences to either true or false-positive populations. "(2) These questions have been researched in two groups, an experimental group, which was diagnosed in the first six weeks of life, and a control group whose results were not given until the child reached four years of age. The results of this study will be coming out in 1995.
Supporters of screening in Colorado were able to lobby their legislators with the organized and impassioned advocacy of the parents and families. It is easy to understand why families of newborns with CF feel so strongly about the screening issue when they are faced with the choice between knowing from the start of their child's life that they have CF or going through weeks or even years of self doubt, disillusionment, and uncertainty in the process of discovering what is causing their child's health problems. The "choice" of whether or not to screen appears self-evident. The families in Wisconsin who fit into the category of those who were not told of their child's screening results until that child was four years old were understandably frustrated. Whether the results were true or false positive, both experienced a great deal of anger and frustration, along with a sincere mistrust of the medical community with whom they had to continue to work. This discontent within the "lay community" presents a strong argument against conducting a blind study in such cases. It would appear that it is quite difficult for families to fully understand the reasoning behind such a long and involved study as opposed to immediate intervention, particularly in light of the fact that the screening program is proactive in nature and is relatively unintrusive and does not cause any physical harm, as with experimentation of new treatments or medications. Therefore, parents feel that the risks should be taken and the screening program implemented. As for families who have false-positive results in the initial screening process, the study has failed to demonstrate any significant long-lasting impacts associated with any false-positive results.
How costs and benefits are prioritized, regardless of the technical data available, appears to be very different depending on where one sits. When attempting to make decisions for entire communities, the struggle lies in whose list or set of conditions carries the most weight. The current decision-making process has resulted in only two state-wide screening programs to date, Colorado and Wyoming, with Wisconsin nearly ready to initiate its program. The other 47 states are still grappling with the issue. It will likely be helpful for states to be able to review the results of Colorado's, Wisconsin's, and Wyoming's data. However, the major issues will still exist, and choices will still need to be made.
The task which lies ahead is the implementation of mandatory screening in the remaining 47 states. Medical advances, as well as the experiences in Colorado and Wisconsin, now provide us with many answers to the questions that have contributed to the controversy and blocked the adoption of screening programs. It is now possible, however, to overcome the conflict that has divided us. Action plans need to be developed in each of the remaining 47 states, which can lead to the development of a broad-based consensus. This consensus can then provide the basis for the passage of working legislation. Let us now turn to the analysis of a specific approach to consensus building and the adoption of mandatory screening legislation.
There is a group in Cambridge, Massachusetts, that is conducting research in a new method of working with groups who appear to be in "intractable" conflict, polarized by different values and sub-cultures. This project has spent much of its time looking into the emotion-filled debate over abortion; however, the theory is applicable to many controversies including CF.
For the purposes of this paper, I will only summarize the carefully structured framework for this approach to communicating. More information can be acquired by contacting the Public Conversation Project. In each state, an organization must make a commitment to convene the Dialogue process. Professional facilitators must be found who will work with the organization to imitate the process. The process begins with extensive preliminary telephone work done by the facilitators and interested parties to prepare for the discussion. Invitations are sent to between six and ten carefully selected representatives from varying perspectives of the debate. The night of the gathering a dinner is first served at which time the group is not allowed to disclose anything related to their position on the issue at conflict. After dinner the group meets with the facilitators and is asked several pointed questions. The group is subject to very rigid guidelines or rules of communication. The objective of this evening is not to get any kind of resolution. There should be no reason for parties to become positional about their discussion. There are no immediate expectations of consensus. This allows the group to avoid any chance of failing to meet unrealistic expectations. The group meets, talks, hopefully listens, and has the opportunity to gain respect for the other individuals' views and motivations.
It would appear that this would be a good tool in reshaping the conflict over screening for CF. If misconception, miscommunication, and lack of respect (real or perceived) exist in this debate, then opening minds by good effective communication should be helpful. This format for discussion can also provide an opportunity to create the group, which will influence the implementation of a screening program, or at least allow for other ideas and approaches to be heard and possibly evaluated. The Dialogue would hopefully be one alternative; however, it was shaped to recognize interests of all the participating parties. Once the Dialogue or discussion process has been formally introduced, there may be more room for negotiation regarding the weightiness of the various costs and benefits and their supporting data leading towards a new kind of decision-making process. The group should continue to meet with the facilitators until a working consensus can be achieved.
The Dialogue process will establish new patterns of relationship among the parties. These patterns are then ready to move into an action phase. This phase will require the development of a committee to influence legislation. The committee needs to gather existing legislation and determine its application to its state. Legislative sponsors must be found. It will be helpful to include these policy makers in the Dialogue process. The committee will then work with legislative sponsors to bring relevant information and testimony to legislative committee hearings. The committee must be able to lobby individual legislators. Effective communication will continue to be helpful when working with legislators in the policy- making process. The strength of the committee will be greatly enhanced if it can speak with a single voice.
The core issue in the debate over screening for CF has been the question as to whether or not there is enough of a direct benefit to newborns with CF and their families to incur the costs involved in a statewide screening of all infants. My analysis leaves little doubt that the monetary cost-benefit ratio is overwhelmingly in favor of screening. A second issue relates to which screening method should be used. Even though the Two-Tiered IRT assay has the disadvantage of a high number of false-positive results in its first two stages of testing, I believe it is the appropriate test to use for mandatory screening. A definitive diagnosis can be made within the first four to six weeks of life. There is little evidence of long-term negative impact that results from a false-positive assay result. The IRT-DNA method of screening is much more costly. It also creates ethical and political controversies, which can be avoided by using the Two-Tiered IRT assay. Finally, while the IRT DNA is extremely accurate, there are so many different geneotypes for CF that it is impossible to test for each one in a statewide screening program of all infants. Therefore, there would be some of the more rare geneotypes that would not be detected in the screening , thereby giving the family a false negative test result. A third issue revolves around the direct medical benefits that may accrue to the child with CF who has been diagnosed through screening. It appears that the use of enzyme supplements provides nutritional support to the child positively affecting their long-term growth and development. In addition, new treatment strategies for the lung disease are being developed and perfected. The isolation of the gene for CF makes gene therapy a reality. When these benefits are contrasted with fears related to potential psychological damage to children and their families, which may result from screening, the medical benefits seem persuasive. This is especially important since the Wisconsin study shows little long-term psychological damage connected with newborn screening.
When weighing costs and benefits on any issue, it is clear that some costs will be incurred and some benefits will be lost. The goal is to reach the most productive balance. Even with years of conclusive data, there will still be those who will maintain ethical, religious, and emotional positions. The struggle which exists with medicine is its innate purpose of healing, caring, and enhancing quality of life, which is often made difficult by the realities of funding, technology, data, and competition. The debate lies in the hands of the interested parties within the 47 states who are continuing to assess the need for a state- wide screening program for CF. Whether they will use their procedural rituals or the dialogue process to work towards that ultimate decision is yet to be seen. I would hope, that whatever process they go through, they continue to look for new ways of communicating and including one another over the old, traditional, more imposing, and less inclusive decision making methods. I am not convinced that in this conflict the basic core issue is the point of intractability, but instead, the lack of movement may lie in the method, the process, and the side issues, which develop and detract. If Dr. Robert Gutherie and the PKU advocates had not fought the social, psychological, and medical norms of the time, the quality of life of those persons affected would be greatly lessened and possibly lost.
My husband and I have two children. Our daughter was diagnosed with CF by the Colorado newborn screening program in April 1994. She was 1 month old. She has been taking enzyme supplements since shortly after we learned of her CF. Due to her early diagnosis, we have had the opportunity to participate in a study which, in part, measures and evaluates the amount of malabsorption she is experiencing. The study targets her progress at 3 months, 6 months, 1 year, and 2 years of age. At her 6-month evaluation she was malabsorpting at 40 percent and her weight had dropped from the fiftieth percentile to below the twentieth percentile. Because of the test results and our close monitoring of her weight gain, it became evident that a change in her enzymes was necessary. After the change her weight increased and returned her to the fiftith percentile. The few colds she has experienced have been treated with antibiotics along with careful monitoring, which has allowed her to have a normal first year. Now into her second year she is a beautiful, independent child who meets all the normal psychological, developmental, and physical requirements of her age.
The newborn screening as the diagnostic process for identifying CF in our daughter was emotional, effective, and, we believe, critical in our successes this first year and beyond. We have had great medical care, education, and support from the CF clinic at the Children's Hospital in Denver as well as from other families touched by CF. Our daughter has had the opportunity to grow well, to develop normally, to breast feed for 14 months, and to receive benefits from participating in research as well as making a contribution to others with her study results. We are a family who has been positively affected by the infant screening process. We did not know before our daughter's diagnosis that CF was or could be a part of our lives. With one in every 20 individuals as carriers of the CF gene, we must all realize the potential for CF in our lives and then respond in such a way that our children will benefit the most. The quality of life in both the short and long run will be greatly enhanced by the ability of all of the parties involved to take responsibility and ownership of the health of our children.
Special recognition for their support, expertise, teaching, and time goes to F. Accurso, M.D.; Meg Anthony, M.S.W.; Guy Burgess; Heidi Burgess; Keith Hammond, M.S.; and Paul Wehr. A thank you goes to Katie Kingston for all of her volunteered reading.
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(1) Funding for this Project was provided by the William and Flora Hewlett Foundation and the University of Colorado. All ideas presented are those of the author and do not necessarily represent the views of the Consortium, the University, or Hewlett Foundation. For more information, contact the Conflict Resolution Consortium, Campus Box 327, University of Colorado, Boulder, Colorado 80309-0327. Phone: (303) 492-1635, e-mail: crc@cubldr.colorado.edu.
© 1994. Conflict Resolution Consortium. Do not reprint without permission.
(2)Audrey Tluczek, et al. (1991), "Psychological Impact of False- Positive Results When Screening for Cystic Fibrosis," Pediatric Pulimonology Supplement 7:29-37.