What is the value for money of prenatal carrier screening for spinal muscular atrophy? Too soon to say.

L ittle et al 1 pose an important question: would the universal offer of carrier screening for spinal muscular atrophy (SMA) during prenatal care be cost-effective, ie, provide good value for money spent? The rapid expansion of the availability of molecular genetic tests for rare disorders, with approximately 1700 tests currently available, poses a challenge to health care providers and payers. We as a society do not have sufficient funds to pay for all possible genetic tests, and prioritization in some form must be undertaken. Little et al and the American College of Obstetricians and Gynecologists are to be commended for addressing the balance of technological opportunity in genetic testing and opportunity cost of scarce health care resources implicit in the concept of cost-effectiveness. The decision analysis prepared by Little et al estimated the net costs of screening for SMA, including reductions in costs of care associated with termination of affected fetuses, relative to gains in maternal quality-adjusted life years (QALYs). The approach used is similar to that used in cost-utility analyses of prenatal testing for fragile X syndrome and Down syndrome, the results of which appear to have gained acceptance in the obstetrics and gynecology literature. However, this approach has inherent limitations. The QALY was developed to measure the combined effects of premature death and disability on individuals who suffer from a disease or injury, and the relatively minor spillover effects on the health of other family members typically are ignored in cost-utility analyses. QALYs are not well suited to capture the personal utility or value either of diagnostic or genetic information in general or of prenatal carrier testing in particular. Because Little et al modeled the effects on only the woman of an affected fetus or child, it is not surprising that the projected gain in QALYs from prenatal diagnosis in their model was extremely modest. However, that is not the only possible method to calculate QALYs. For example, using a time-tradeoff method to assess the utility of prenatal screening for Down syndrome, Harris et al found that the QALYs associated with reassurance to women with normal findings dominated the negative effects of positive amniocentesis results. Similar results were found in another study that used the theoretically preferable standard gamble method to evaluate carrier testing for cystic fibrosis (CF). Had Little et al incorporated the same assumed utility of negative carrier test results for SMA as previously estimated in these studies of testing for Down syndrome or CF, the projected QALY gains, and hence the cost-effectiveness of the screening, would have appeared more favorable. It should be noted, however, that the value of reassurance from testing for an additional disorder during pregnancy can be determined only by asking women their perceptions about screening for multiple conditions. The other major drawback of the approach used by Little et al was its emphasis on financial cost savings resulting from the early diagnosis and termination of affected fetuses. This general approach long has been criticized by health economists as inconsistent with economic theory. It implicitly prioritizes testing for disorders that have high lifetime medical costs, such as CF, over disorders, such as SMA, which typically result in early death and, hence, low lifetime medical costs. The prevention of diseases that are fatal in early childhood and have no treatment saves little money relative to disorders that are disabling but not lethal. The results of a standard cost-effectiveness or cost-utility analysis of prenatal carrier screening are greatly influenced by the projected financial savings to the health care system resulting from the termination of affected fetuses. Such an analysis places little or no value on the ability of parents to prepare for the birth of an affected child, to avoid lengthy diagnostic “odysseys,” or to plan future childbearing. The justification of screening as cost-effective based on the frequency of terminations can seem difficult to reconcile with the clinical genetics paradigm of nondirective offer of counseling, carrier testing, and prenatal diagnosis. A simpler economic approach– cost-comparison analysis– calculates the cost per carrier or case detected for different testing strategies. Carrier testing for SMA presumably costs more per case detected than does screening for CF because of the lower prevalence of SMA. The cost-comparison approach leaves it to policy makers to value the detection of carriers. Policy makers may consider the opportunity for informed choice by parents and the seriousness of the disorder as well as the potential reduction in health care costs. In addition to the numbers of cases detected, analysts should report the numbers of false-positive, false-negative, and true-negative test results and stakeholders also should take into account such outcomes of testing and their valuations. From the Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA. Reprints not available from the authors. The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention. 0002-9378/free Published by Mosby, Inc. doi: 10.1016/j.ajog.2010.01.031