A new study could identify ways to improve the way chromosomal microarray test results, especially findings of uncertain significance, are communicated to the parents of children with autism spectrum disorder.
The National Institutes of Health this month awarded $240,000 to researchers at the University of Pennsylvania to support the project. Marian Reiff, a research associate at UPenn's Center for the Integration of Genetic Healthcare Technologies, will lead the effort. She told BioArray News this week that the grant is "sufficient" to fund the project to its conclusion, expected at the end of 2014.
Since Reiff joined CIGHT three years ago, she has been studying the meaning and impact of genome-wide array-based testing for children and families. This work has resulted in a number of publications. Reiff, who has a background in sociomedical sciences, anthropology, and social work, said that studies to date have identified the need for in-depth genetic counseling before and after testing, to "prepare families, respond to questions, and clarify the results."
She said that this new study of parents of children with ASD who have undergone microarray testing will describe "parents' perspectives of the testing experience, the perceived utility and value of test results, and the psychosocial implications of uncertain results."
The team's findings will be used to "improve the process of pre-test consent, to inform educational materials for families and providers, and for training of clinicians offering chromosomal microarray analysis as part of the protocol for ASD diagnosis," Reiff said. "We also hope to develop interventions to foster improvement in parents' experience of testing and understanding of results and to test the effectiveness of these interventions in future research," she added.
The sample for the new study will consist of parents of children with ASD who have undergone testing at the Children’s Hospital of Philadelphia's cytogenomics laboratory. Its director, Nancy Spinner, and genetic counselor Surabhi Mulchandani will help to obtain contact information for the patients' families. Then the parents will be contacted and asked if they are interested in participating in an interview, Reiff said.
There are three other co-investigators on the project, Reiff noted: Barbara Bernhardt, co-director of CIGHT; Pamela Sankar, associate professor of bioethics at UPenn; and Ellen Giarelli, associate professor in the doctoral nursing program at Drexel University.
Reiff joined CIGHT in 2008, the same year that she became aware of the growing use of arrays to diagnose constitutional abnormalities in children. Within CIGHT, she received support to explore the implications of receiving microarray test results and the uncertainty that the results create for patients, their families, and their healthcare providers.
"In most of my research I use a combination of qualitative and quantitative methodologies," said Reiff. Qualitative methods employed have included interviews that later undergo content analysis. Quantitative methods have included online surveys of clinicians that offer array-based testing.
While Reiff's research has focused on chromosomal microarray analysis in general, she decided to focus on ASD in this particular study because it is "one of the most common serious developmental disorders," and found in almost 1 percent of children in the US.
Array test results fall into three categories: negative, or normal; positive for a deletion or duplication known to cause pathology, or abnormal; and ambiguous, meaning the presence of a variant of unknown clinical significance.
For the current study, Reiff's team will rely on qualitative methods. She intends to interview 60 parents of children with ASD who have been tested by chromosomal microarrays: 20 parents of children with results in each of the three categories — normal, abnormal, and ambiguous.
According to the grant's abstract, the researchers will conduct "open-ended, semi-structured telephone interviews" and use grounded theory and content analysis to analyze the perspectives of parents regarding the testing experience and impact of test results.
The aims of the study are to describe parents' experiences of testing including expectations of what chromosomal microarray analysis might provide, understanding of results, perceived value of the test results, perceived benefits and harms, and use of results in decisions about the child's medical and educational options, according to the abstract.
Reiff's team also aims to explore the psychosocial implications of uncertain results, and whether the results have influenced the way parents cope with having a child with ASD. The researchers will focus on "parental uncertainty, stress, stigma, self-blame, hope, and sense of control in relation to the child's condition," and examine similarities and differences based on type of result, socio-demographic background, and length of time since testing.
Ultimately, the team will identify challenges and ways of coping that the parents of children with ASD tested by chromosomal microarray analysis find effective, the researchers said in the abstract. Based on its findings, the team will also make recommendations on how to "improve communication about genetic test results, address the stressful aspects of testing, and suggest effective ways" to deal with the uncertainty associated with chromosomal microarray analysis.
'Domains of Understanding'
The team made similar recommendations in a paper published in Genetics in Medicine last month.
For that paper, which was not limited to ASD, the authors conducted semi-structured interviews with parents of 25 pediatric outpatients with chromosomal microarray test results indicating either a pathogenic alteration or a variant of unknown significance.
The team identified three "domains of understanding:" comprehension of test results; interpretations of scientific uncertainty; and personal meaning for the child and family. Incomplete comprehension of test results and scientific uncertainty were "prominent themes" for families receiving results, according to the paper. Receiving results from non-geneticists and by telephone, long waits to see a geneticist, and misleading Internet searches also contributed to misunderstandings.
Reiff said that parents of children who have been tested "need guidance" when using the Internet. "Since the results are often rare, novel, and can be ambiguous, there may not be much information available and it is possible to find misleading information about very severe cases based on similar but not identical genetic information," she said. "This can lead to unnecessary distress for families."
In response to this issue, Reiff said that counselors need help to clarify the search terms and the websites that should be used to find reliable information and to connect with other families. "Our studies also suggest that results should be provided to families by professionals with genetics expertise, in order to reduce the confusion that can arise as a result of ambiguous results," she said.
Reiff said she now hopes to provide similar recommendations for parents of children with ASD who have undergone array-based testing. "By applying models from social science theory it is possible to differentiate domains of understanding and to identify several domains where uncertainty can be reduced," she said. "In this way, it may be possible to improve parents’ understanding of their microarray results, even though there is still scientific uncertainty."
Another paper describing the perspectives of physicians who have ordered microarrays in pediatric populations is currently under review, she added.
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