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SUPPLEMENT ARTICLE |
a Genetic Disease Branch, California Department of Health Services, Richmond, California
b Public Health Institute, Berkeley, California
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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METHODS. In April 2004, a 10-question survey was mailed to 106 individuals identified as key newborn screening contacts in each state. The survey requested information on issues that affected the state's ability to expand newborn screening to include MS/MS technology.
RESULTS. Representatives from 51 of 53 states/territories responded to the survey. Of the 51 responding states, 32 (63%) said that they are offering MS/MS screening currently. The top 2 issues that most affected the ability of states to add MS/MS screening were difficulty acquiring support within the organization (66%) and funding limitations (63%). The screening criteria that were most difficult to address were knowledge about the natural history of MS/MS-detectable disorders if untreated (37%), the short-term costs of screening and diagnosis (36%), and the long-term follow-up costs (34%). The top-ranked laboratory issues were the high costs of equipment and supplies (53%) and the development of appropriate population-specific cutoff values (41%). The top-ranked follow-up issues were the availability of accepted protocols and guidelines for MS/MS diagnostic evaluations (59%) and the availability of adequate educational materials describing the disorders (44%).
CONCLUSIONS. Several of the issues identified can be addressed through improved, more-comprehensive, patient surveillance systems that track patient health status and health services utilization, although other approaches need to be developed. Through a better understanding of these issues and challenges, the community of professionals who are concerned with the quality and scope of newborn screening may be better able to help states develop strategies to overcome these barriers.
Key Words: newborn screening • tandem mass spectrometry • program implementation
Abbreviations: MS/MS—tandem mass spectrometry
With the advent of tandem mass spectrometry (MS/MS), there is now the capacity to screen for many more metabolic disorders with the same newborn blood specimens that are collected routinely, by state-based newborn screening programs, from all infants born throughout the country. This new technology has brought with it unique program development and implementation challenges. A slow but gradual trend has emerged as more states take on this challenge and expand their newborn screening programs to include the detection of disorders with MS/MS technology.1–3
In recent years, the popular press4–6 and the Wall Street Journal7,8 covered stories that raised the public's awareness about the discrepancy in the numbers and types of disorders that are screened for by state newborn screening programs throughout the nation. Advocacy groups, including the March of Dimes9 and the Save Babies Through Screening Foundation,10 have also been instrumental in bringing to the public stories that highlight the unnecessary tragedies faced by families whose infants were born in states lacking MS/MS technology. In contrast, the stories of families whose infants were born in states offering MS/MS screening highlight the life-preserving successes of early diagnosis.
This media coverage coincided with the September 2004 briefing of the much-awaited report by the American College of Medical Genetics,11 which recommended that states expand their newborn screening programs to include a minimum of 29 primary disorders, including 20 disorders identifiable through MS/MS screening. As a result, state newborn screening programs have come under increased pressure to expand their programs to incorporate MS/MS screening. To obtain a better understanding of the issues and challenges associated with implementing MS/MS screening technology, a national survey was undertaken to identify the unique issues and barriers faced both by states that have already implemented MS/MS screening and by states that have not yet done so.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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The first section of the survey confirmed the contact information for the respondents and requested clarification regarding whether currently their state was offering MS/MS screening and, if so, whether screening was offered as part of a universal (mandated) program or as a supplemental (voluntary) test. Respondents from states not offering MS/MS screening were asked whether they planned to offer screening in the future and, if so, whether screening would be universal or supplemental. For current and future programs, respondents were asked to provide information about the number of MS/MS-detectable disorders that are or would be included in the screening panel.
The core section of the survey required respondents to rank a list of issues according to how much the item affected their state's ability to expand newborn screening to include MS/MS-detectable disorders. Respondents were then asked to rank the criteria they used when determining what new disorders to add to their screening program and were asked to indicate which of these criteria had been especially challenging to address in the context of MS/MS screening. Next, we presented a list of laboratory and follow-up issues and asked respondents to rank the issues according to how much difficulty or delay these issues created during planning of a new program. After marking and ranking of the priority issues, several open-ended questions were posed to ascertain any additional barriers or challenges that had not been explicitly addressed in the survey.
For each question posed, we report the issues that were mentioned most frequently within each priority rank (eg, rank 1, rank 2, and rank 3 categories). Because many issues ranked close together, we also report the top issues that emerged after we collapsed the top 3 ranks into 1 category.
Another approach to analyzing the data was to develop a single priority score for each of the issues listed for each question. In this way, we could determine which issues had statistically different scores, compared with any other issue, and assess whether some issues clustered together in priority order. To achieve this, we recoded the responses to make the rank a continuous variable, so that higher rank scores represented issues of higher priority to the respondents. This involved reversing the ranks. As an example, for a question that had a choice of 6 issues, any rank 1 issue was recoded as 6 and any rank 6 issue was recoded as 1; a blank (no response) was recoded as 0. If no responses were given for an entire question, then we coded the response as missing. Then a weighted score was developed; we multiplied the number of survey respondents who chose a specific rank for an issue and divided this sum by the number of individuals who responded to the question. This number takes into consideration the range of all responses to each issue and provides a single score for comparison purposes. We used the Waller-Duncan K ratio test to determine which priority scores were significantly different, with the Proc GLM procedure (SAS Institute, Cary, NC). First the results of this analysis were analyzed as a group of all respondents combined. Next we stratified the respondents into 2 groups and used binomial analysis to test whether the responses from states not yet offering MS/MS screening were statistically different from responses from states already offering MS/MS screening. Lastly, we used 
2 analysis to compare responses from states that indicated they were not planning to implement MS/MS screening with responses from the group of states that said they were planning to offer or were currently offering MS/MS screening.
Although 2 people from each state were sent the survey, only 1 person responded in most cases. If both respondents for states with 2 survey respondents ranked the same issue, then we took the average rank for that issue, to correct for any potential bias that could result from having any single state over-represented in the ranking scheme. Although the responses to this survey represent the impressions of knowledgeable individuals working in state programs, they cannot be interpreted as the official positions of those agencies.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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20 MS/MS-detectable disorders, including 7 states (22%) that screened for 10 disorders. As shown in Table 1, 35% of respondents ranked "funding limitations" as the top limiting factor in including MS/MS screening. When responses for the top 3 ranked issues were collapsed, "acquiring support within your organization" emerged as the top issue (66%), followed by "funding limitations" (63%) and "advisory board recommendation required" (60%).
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Among the choices of screening criteria that had been especially difficult to address in the context of preparing for MS/MS screening, the top-ranked issue was the need for information about the "costs of screening and diagnosis" (27%). When the top 3 ranked issues were collapsed, "knowledge about the burden of disease if untreated" (37%) ranked as the top issue, followed by "costs of screening and diagnosis" (36%) and "costs of follow-up" (34%).
Regarding laboratory issues, the top-ranked single issue was the "high costs of equipment and supplies" (44%), and this remained the top issue when the top 3 ranked issues were collapsed (53%). "Developing appropriate analyte cutoffs for your population" and "availability of trained laboratory staff" ranked next as priority issues (41% and 39%, respectively) when the top 3 ranks were collapsed.
The follow-up issue that was mentioned most often in the priority 1 rank was "accepted protocols and guidelines for diagnostic workups" (26%). This was also the top issue when the top 3 ranks were collapsed (59%). The next most important follow-up issues (top 3 ranks collapsed) were "availability of adequate educational materials describing disorders" (44%) and "resources and staff for adequate long-term patient tracking" (35%).
The binomial analysis was conducted to determine whether specific issues were more likely to be mentioned by states offering MS/MS screening, compared with those not yet offering screening, regardless of how the specific issue ranked. States already offering MS/MS screening were most concerned with "validation of cutoff values with known diagnosed cases" (P < .01), "determination of ‘presumptive positives’ for referral to metabolic specialist" (P < .02), "accepted protocols and guidelines for diagnostic workups" (P < .03), and "unacceptable equipment downtime for maintenance" (P < .05). States not currently offering MS/MS screening were most concerned with "costs of follow-up" (P < .001), "test feasibility for population screening" (P < .02), "access to treatment and clinical management services after diagnosis" (P < .04), and "availability and access to appropriate follow-up centers/specialists" (P < .01). Among respondents from the 5 states not planning to offer screening (or not yet decided about whether to offer MS/MS screening), the single issue that emerged as statistically significant was "availability and access to appropriate follow-up centers/specialists" (P = .05).
Table 2 shows the top issues with the weighted-score approach. The issues are listed from highest weighted score to lowest weighted score for each question. The weighted ranks are listed with the scores. Issues that fall within the same cluster can be interpreted as having the same priority score as the other issues in the group. For example, for question 1, "funding limitations" ranked as the top priority issue, but statistically the weighted score clustered with the weighted scores for the issues "acquiring support within your organization" and "advisory board recommendation required." For the next question, the issues that emerged as separate and statistically unique were "benefits of early intervention to the newborn" and "screening test sensitivity and specificity." The issues that fell between ranks 3 and 8 were part of a cluster and therefore can be interpreted as being within the same priority category. The final 2 issues, ie, "benefits of early diagnosis to the family" and "costs of follow-up" ranked last in importance and were part of a statistically unique cluster.
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Table 3 presents the average scores and weighted ranks among states already offering MS/MS screening, compared with states not currently offering MS/MS screening. Both groups of respondents ranked "benefits of early intervention to the newborn" as the number 1 criterion for determining which new disorders to add to their screening program, and both groups ranked "costs of screening and diagnosis" and "costs of follow-up" as the number 1 and number 2 issues, respectively, when asked which issues were most challenging to address in the context of MS/MS screening. Beyond these similarities, other issues emerged with different priority orders. For example, the number 1 issues for states not yet offering screening were "funding limitations," "high costs of equipment and supplies," and "availability and access to appropriate follow-up centers/specialists." The number 1 issues for programs currently offering MS/MS screening were "acquiring support within your organization," "developing appropriate analyte cutoffs for your respective population," and "accepted protocols and guidelines for diagnostic workups."
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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20 MS/MS-detectable disorders. An up-to-date account of how many disorders are being screened for by different states is available at the National Newborn Screening and Genetics Resource Center Web site (www.genes-r-us.uthscsa.edu). This survey identified important issues and challenges that need to be addressed so that the goal of a uniform panel of disorders across all states can be achieved. Although lack of organizational support and funding were identified as major barriers to MS/MS screening implementation, support for MS/MS screening will likely increase in the future if programs develop strategies to address the other issues and challenges that were identified.
From the laboratory perspective, in addition to needing funds to pay for the high costs of equipment, survey respondents indicated the need for guidance about how to develop and to refine appropriate cutoff values for their respective populations. The best way to refine cutoff values is for states to be able to screen as many known diagnosed cases as possible. This will require improved surveillance systems to identify all affected cases and exchange of specimens with other states. Knowing which cases were identified successfully through screening, as well as which cases were missed, is critical to refining analyte cutoff values. More-efficient analyte cutoff values would improve the screening test sensitivity and specificity, would result in fewer false-positive results, and ultimately would improve the performance of and support for MS/MS screening.
Once adequate case-reporting systems are established, programs should set up detailed, long-term, patient-tracking systems. Patient-tracking systems would help address several issues identified in this survey, ie, the need for more information about the natural history of MS/MS-detectable disorders, the need for guidelines and protocols for case management, and the need for data about the short-term and long-term costs of screening. These goals can be achieved through patient-tracking systems that focus on documentation of the health status of the child, as well as documentation of data on health service utilization.
Documentation of the health status of the child, preferably over the child's lifespan, would help address the need to know exactly how infants benefit from early detection of asymptomatic, MS/MS-detectable disorders. The lack of information about the long-term outcomes of children identified through screening, compared with those identified on the basis of symptoms, is an issue that has been raised by others.20,21 This is particularly true for rare disorders for which the natural history is not well known.
Patient-tracking systems should also incorporate data on health service utilization. Service utilization data should focus on what tests were ordered, under what circumstances they were ordered, and what outcomes were achieved. Short-term service utilization data should monitor presumptively positive cases, to document all services required to confirm or to rule out a diagnosis. After a diagnosis is determined, patient-tracking systems should continue to collect data on services provided and patient health outcomes. This information could help guide the development of clinical guidelines for care and follow-up protocols. If these data include cost information, they could be useful in establishing the short-term and long-term economic impacts of MS/MS screening.
The need for increased availability of staff members trained in the intricacies of MS/MS screening was identified from the laboratory and follow-up perspectives. The specialized staff training programs developed recently at Duke University and Baylor University is a good first step. In response to one of the open-ended questions, 15% of respondents said that their states relied on these training programs to meet their staff training needs. Over time, the number of people with specialized MS/MS training is likely to increase. In some cases, it may be helpful for more-experienced states to mentor less-experienced states. State legislatures may want to consider contracting with other states that have already established the technology, if it is not feasible to develop their own programs.
Lack of appropriate educational materials describing MS/MS-detectable disorders was also identified as an important issue. Development of new materials for parents and providers is critical to the successful implementation of MS/MS screening programs, and it is likely that adequate materials will become available with time.
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CONCLUSIONS |
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ACKNOWLEDGMENTS |
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Many thanks go to the participating investigators Robert Currier, PhD, George Cunningham, MD, MPH, Martin Kharrazi, PhD, Fred Lorey, PhD, and John Sherwin, PhD, for providing valuable feedback in the design of the survey and analysis of the data.
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FOOTNOTES |
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Address correspondence to Lisa Feuchtbaum, DrPH, MPH, Genetic Disease Branch, California Department of Health Services, 850 Marina Bay Pkwy, F175, Richmond, CA 94804. E-mail: lfeuchtb{at}dhs.ca.gov
The authors have indicated they have no financial relationships relevant to this article to disclose.
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