Our study shows that screening for SCID is likely to be cost-effective because the condition is rare, limiting the overall number of infants requiring treatment, and because of better health outcomes and lower costs associated with earlier HCT. Cost effectiveness of screening for SCID compares favorably with cost-effectiveness of other health interventions: $28,000 per QALY (based on the initial assumptions) would be considered moderately or highly favorable based on the scale proposed by Weinstein et al[27
]. Screening appeared cost-effective for test costs up to $50, if all other variables are constant. Our estimates are similar to ICER between no screening and universal screening for other newborn metabolic diseases (ICER of $5,800 to $42,000/life years) or sickle cell anemia (ICER of $13,000/life years saved) [28
Incidence of disease and specificity of the screening test greatly influence cost-effectiveness. As expected, our model showed that higher incidence predicted greater cost-effectiveness of screening. Cost effectiveness was also sensitive to test specificity: ICER rose beyond $50,000 when specificity was less than 0.94. However, the range of acceptable test specificity was dependent on the underlying incidence of SCID. In summary, factors influential to the cost-effectiveness are the cost and specificity of the test and diagnostics, the incidence of disease (at extremes), and the improved health outcomes.
McGhee et al. previously examined potential costs and benefits of newborn screening for SCID using a hypothetical two-tiered testing protocol based on a proposed IL-7 assay (which to date does not have analytical validity) and a TREC assay [30
]. They suggested an initial IL-7 assay followed by TRECs for the 4% of positive IL-7 specimens. This strategy was estimated to be 99.6% sensitive, 99.1% specific, and cost effective if test costs were less than $5. Our results create an even stronger case for SCID newborn screening by TREC assay alone, which we predict to be cost-effective with a test specificity as low as 94% with a similar test cost of $4.22.
Furthermore, because we modeled the natural history of SCID using stochastic probabilities to represent real-life case scenarios of late (Model A) vs. early (Model B) diagnosis, we could incorporate the reduced costs attributable to screening of needing less care in pre-diagnosis and pre-HCT states as well as avoiding the infections that increased hospitalization duration. Finally, unlike McGhee’s deterministic model based on an average life-span of the individual with SCID, our model considered the magnitude of reduced care costs over time. Both models reached the conclusion that screening for SCID is cost-effective.
Modeling requires simplifying assumptions about costs of testing and healthcare that could impact the validity of our results. We considered only laboratory costs of SCID screening integrated into an existing screening program without additional administrative services, sample collection or follow-up. Assumptions were also made in classifying the course of SCID using a limited number of health states and a single HCT. In reality, early and late HCT costs vary between institutions and depend on many patient and donor factors. However, our analysis tended to minimize the differences between early and late HCT, but still predicted newborn screening for SCID to be cost effective. When more specific actual data on costs and outcomes are available, these can be used to refine our model. Although our survey provided valuable insights and was in agreement with published outcome information from several studies [31
], our set of subjects may not have represented SCID patients overall. To minimize these limitations we used conservative values for key variables affecting the cost effectiveness of screening and explored the impact of varying these estimates using sensitivity analyses.
Our modeling indicates that the cost-effectiveness of TREC screening for SCID compares favorably with screening programs for other rare conditions as well as common diseases such as prostate cancer [34
]. The benefits may be enhanced because the TREC assay detects non-SCID T cell lymphocytopenias in addition to SCID, such as DiGeorge syndrome, which are detected by low TRECs, as described in the first year of statewide TREC screening in Wisconsin [31
]. These disorders would be differentiated from each other and from SCID through the confirmatory testing process and early intervention could lead to better outcomes. Indeed, immunologists agree that profound T lymphocytopenia from any cause places infants at risk for severe infections [35
]; early diagnosis through screening could prevent infections through use of prophylactic antibiotics and immunoglobulin as well as avoidance of live attenuated rotavirus vaccine, a cause of infectious diarrhea in immunocompromised infants [32
Our approach can be generalized for modeling natural histories of subject cohorts along multiple alternative paths in other health conditions. Markov models reflect different possible health states and incorporate information about cohort histories into decision analysis, making possible evaluation of cost effectiveness of interventions that have complex influences on disease course and healthcare costs.
Implementation of neonatal screening for SCID has evolved rapidly. In 2007, a SCID working group convened to discuss requirements for large-scale studies [36
]. Wisconsin initiated the first state-wide trial of TREC screening, finding excellent sensitivity, while specificity, particularly in preterm infants, could benefit from refinement [37
]. Recent Wisconsin TREC assay specificity has increased to 99.983% at an average cost of $6.00 per sample [38
]. In 2009, Massachusetts began a state-wide pilot of TREC screening and has reported successful identification of a patient with SCID [9
]. Based on an evidence review [39
], recommendation of an expert advisory committee, and the recommendation of the Department of Human and Health Serivces Secretary that SCID be added to the uniform panel of screened contitions, California, New York, Louisiana, Puerto Rico and other States are conducting SCID screening, and additional cases of SCID and T cell disorders have been found [J. Puck, unpublished data]. Follow up of the outcomes of these programs will provide direct information to evaluate cost effectiveness of SCID screening and to refine the model presented here.