Screening for medium chain acyl-CoA dehydrogenase deficiency has still not been evaluated

EDITOR—In effect, Tanner et al note that the glass is
half-empty in the complete evaluation of the effectiveness of screening
neonates for medium chain acyl-CoA dehydrogenase (MCAD) deficiency.¹
Evaluation of population-based screening is a two-part process. First, one
assesses the likely benefits and costs before introduction. Second, one
subsequently investigates whether these calculations are borne out in practice.
The UK health technology assessment (HTA) process has undertaken the first step
of this evaluation process, to assess the likely benefits and costs. Two HTA
systematic reviews concluded that medium chain acyl-CoA dehydrogenase
deficiency fulfils “all”² or “most”³ of the criteria for
a screening programme. The one criterion not clearly satisfied is that the
natural history of the disorder is well-defined. Yet the only practical way to
gather the population data needed to calculate the long-term benefits of
screening for this disorder is through population screening using tandem mass
spectrometry (MS).^{3, 4} The first of the HTA reviews called for a
large-scale pilot study using tandem MS to establish technical robustness,
screening and diagnostic criteria, and general practicability, as well as to
document the effectiveness of neonatal screening using tandem MS for a range of
conditions, not just MCAD deficiency.²  

Several newborn screening programs in the United States and
other countries have introduced tandem MS on a pilot basis within limited
geographic areas. Tanner et al object that this is tantamount to tandem MS
being “introduced without trials.”¹ A pilot study is not the same as
a randomized trial. The purpose of a randomized controlled trial is to
establish clinical efficacy. In contrast, a pilot study is intended to work out
logistical and practical issues under routine programme conditions prior to
implementation on a larger scale as well as to compile data on outcomes in a
defined population. For example, the state of Massachusetts has introduced
tandem MS on an investigational basis,^{with screening for MCAD
deficiency conducted on the same basis as for established conditions, while
screening for other conditions detectable through tandem MS is performed on an
investigational basis.5 The data currently being collected in
Massachusetts and elsewhere should satisfy most of the specific aims for the
pilot study of tandem MS based screening recommended by the HTA review.2} 

1.     
Tanner S, Sharrard M, Cleary M, Walter J, Wraith E, Lee P, et
al. Screening for medium chain acyl-CoA dehydrogenase deficiency has still not
been evaluated. BMJ 2001;322: 112.  (http://www.bmj.com/cgi/content/full/322/7278/112)

2.     
Pollitt RJ, Green A, McCabe CJ, Booth A, Cooper NJ, Leonard
JV, et al. Neonatal screening for inborn errors of metabolism: cost, yield and
outcome. Health Technol Assess 1997; 1(7): 1-202[Medline]. (www.hta.nhsweb.nhs.uk/)

3.     
Seymour CA, Thomason MJ, Chalmers RA, Addison MJ, Bain MD,
Cockburn F, et al. Neonatal screening for inborn  errors of metabolism: a systematic review. Health Technol Assess
1997; 1(11): 1-95[Medline].   (www.hta.nhsweb.nhs.uk/)

4.     
Wang SS, Fernhoff PM, Hannon WH, Khoury MJ. Medium chain
acyl-coA dehydrogenase deficiency (MCADD). Genetics in Medicine 1999;
1:332-339. (http://www.cdc.gov/genetics/hugenet/reviews/MCAD.htm)

5.     
Atkinson K, Zuckerman B, Sharfstein JM, Levin D, Blatt RM, Koh
HK. A public health response to emerging technology: expansion of the
Massachusetts Newborn Screening Program. Public Health Rep 2001. In press.