Review of Economic Evaluations on Genetic Diseases
James Jarrett and Miranda Mugford
Genetic technologies often grab headlines and are commonplace in health services
across the world. This working paper is a result of a critical review of the literature .
While the critical review paper focuses on the economic methods used in the evaluations,
this paper will focus specifically on the disease areas in which we found full or partial
economic evaluations and give a critical summary of the results. If you are interested in
the economic methods paper, please do not hesitate to contact the authors.
An online search strategy was developed to find as many economic evaluations of
genetic technologies as possible between the years of 1983 and 2005. The time limit was
included as a result of a previous unpublished study by Ann Raven  that found no
evaluations before 1983. The papers were then reviewed and classified by JJ, using
techniques developed by the NHSEED and the BMJ Working Party . For more
specific information on the methods used, please contact the authors.
There were 378 original articles retrieved from our search. Of which, only 37
were found to be full or partial economic evaluations. Of these, 33 focused on specific
diseases. The remaining four papers looked at multiple disease types. Breast, ovarian, and
colorectal cancer are the most commonly evaluated (accounting for 27% of papers
covering distinct disease conditions). Neonatal and prenatal screening techniques for
Cystic Fibrosis and Down Syndrome are also commonly covered (18% and 15%,
respectively). There are also substantial amounts written on various metabolic, blood, and
Most of the economic evaluation studies on cancer and genetics focused on cost-
effectiveness of different techniques of screening. There are five studies examining the
effectiveness of screening for familial breast and ovarian cancer (associated with
causative mutations in BRCA1 and BRCA2). In an American setting, Tengs and Berry 
found that screening for gene mutations was only cost-effective in populations who
already had a higher risk of having the mutation. The authors concluded that a screening
programme targeting an average risk population would not be very cost-effective due to
the low penetrance of the mutation in the average population. Eccles and colleagues 
found that this was also the case in the UK. Grann and colleagues  found that it is
likely to be cost-effective to screen the Ashkenazi Jewish population for BRCA1 and
BRCA2 mutations within the US.
Heimdal  and Brain  and their colleagues compared different types of
screening programmes for breast cancer. Heimdal and colleagues found that, in Norway,
both the traditional cancer family clinic strategy (pedigree analysis of patients with family
history of cancer) and genetic testing for BRCA1 mutations were cost-effective (the
author‟s compared the strategies to one another, but noted that the traditional clinic has
not been evaluated sufficiently, and that possibly „no surveillance‟ may be a good
comparator to use instead). However, because the cancer family clinics were already in
place, they would be more convenient for the Norwegian health service. Brain and
colleagues looked at the problem in a slightly different way. Their study was carried out
in the UK (Wales) and analysed the health and psychological benefits associated with
multidisciplinary genetic screening techniques versus traditional screening for breast
cancer. The authors found that the multidisciplinary approach was only marginally
Reyes and colleagues  reported a cost-effectiveness study comparing different
methods of screening for hereditary nonpolyposis colorectal cancer (HNPCC) within the
UK. The authors found that a mixture of using the Amsterdam criteria (a family history
based approach) and microsatellite instability (MSI) method of screening was the most
cost-effective in identifying cases of predisposition to HNPCC. This was because
although the Amsterdam Criteria is a very cheap method, it is least sensitive in detecting
carriers. The MSI method is the most expensive, but captures the proportion of carriers.
This seems supported by a study in the USA by Brown and Kessler  which finds that
general population screening is only cost-effective for identifying predisposition cases
when subjected to very restrictive assumptions (such as penetrance of the HNPCC
genotype being at least 80%, and a 100% accuracy of the genetic test).
Ramsey and colleagues  found that, in the USA, MSI screening on patients
with newly diagnosed colon cancer, together with a personal and family cancer history, is
cost-effective for identifying cases of HNPCC versus no screening and becomes even
more cost-effective if the siblings and children of mutation carriers are identified and
screened. Vasen and colleagues  carried out a study in the Netherlands on the cost-
effectiveness of HNPCC surveillance using colonoscopy, and found that when compared
with no surveillance, the benefits (increased life expectancy of approx 6.9 years) are
achieved at costs of US$9,859 when discounted at 5% in 1998 dollars. However, the
authors did not perform any synthesis of costs and benefits.
Chikhaoui and colleagues  compare two screening strategies (clinical
screening vs. genetic testing) for familial adenomatous polyposis (FAP) detection. The
authors find that compared to clinical screening (using family history and pedigree
analysis), predictive genetic screening is the least costly in Quebec. However, the costs to
the health system are minimised by starting the screening on the population at an earlier
Murray and colleagues  carried out a HTA of screening programmes for
Cystic Fibrosis (CF), a disease that affects approximately 1 in 2000 human births in which
the mucus secreting glands become fibrous. Within the review of the health economic
literature they found that a number of researchers (15-17), have found that a combination
of prenatal and antenatal screening was the most cost-effective way to screen for CF.
Effectiveness of antenatal programmes in these evaluations was usually measured as
number of affected pregnancies avoided (aborted), or number of carriers detected. The
cost-effectiveness of screening programmes seems to be very sensitive to changes in
assumptions on the birth of „replacement‟ children, costs of the DNA test, and whether the
study takes into account screening past the initial foetus (for subsequent pregnancies).
However, in Denmark, Nielsen and Gyrd-Hansen  carried out a cost-effectiveness
analysis which found that introducing a prenatal screening programme could lead to a net
cost saving from both a societal and health service perspective, whether or not a
replacement child is born. In their analysis, costs per CF patient ranged from
US$266,990-$303,398 over their lifetime, whereas estimated benefits for avoiding a case
of CF ranged from US$254,854-$533,980 (using OECD PPP  indexed to 1999 prices,
originally reported in Danish Kroner).
Four out of the five studies on antenatal screening programmes for Down
Syndrome (DS), the most common human chromosomal abnormality (trisomy 21),
compares different types of antenatal screening programmes. The technologies used in
these screening programmes were chorionic villus sampling (CVS), amniocentesis,
genetic counselling with amniocentesis, and genetic ultrasound.
DeVore and colleagues carried out two separate cost-effectiveness analyses for
genetic ultrasound (referred to as „sonography‟ in the papers) technology. One analysis
covered a population of women under 35, and the other women over 35 [20,21]. In the
study for women under 35, the authors found that genetic sonography is cost-effective for
both high- and medium- risk patients. For those over 35, genetic sonography followed by
amniocentesis was cost-effective. However, in another study, Vintzileos and colleagues
 found that the benefits of first trimester genetic sonography depended on diagnostic
accuracy. The authors found that, in their setting (a hospital in the USA), there were
potential savings of $22 million for the hospital if the genetic ultrasound was 100%
accurate. Evans and colleagues  also found that specificity of the test was a key factor
in cost-effectiveness when comparing multiples of median and discriminant aneuploidy
Only one evaluation compared the cost-effectiveness of screening programmes
across international lines . That evaluation compared the costs and benefits of DS
screening strategies using nuchal translucenscy thickness (British approach) or maternal
age and maternal serum screening (American approach). The authors concluded that
financial costs of the two systems were only comparable if the first trimester ultrasound
had a sensitivity of 80% and a false-positive rate of 5% in detecting DS and that the
British strategy does not look to be beneficial in the US under any circumstances.
The literature on hemochromatosis (a hereditary disorder characterised by
abnormal deposits of iron in the liver, heart, pancreas, and other organs) in this review is
limited, but Adams and Valberg  conclude that when compared to no screening,
genotypic screening of voluntary blood donors generates a cost-utility of US$20,042 per
QALY gained, and that the optimal strategy for the population in their study was that of
phenotyping with confirmatory genetic testing. The authors found that the model is very
sensitive to the price of the genetic test. If the test costs more than US$28, using
genotyping alone is not cost-effective. El-Serag and colleagues , find that genetic
testing for the hemochromatosis mutation in siblings and children of affected patients is
cost-effective versus no screening regardless of the cost of the test.
In a HTA on Familial Hypercholesterolaemia (a disease caused by mutation in the
low density lipoprotein receptor gene resulting in high levels of plasma cholesterol which
can cause coronary heart disease) Marks and colleagues , set out to “assess the cost-
effectiveness of strategies to screen for and treat familial hypercholesterolaemia.” The
authors identified several screening strategies including universal population screening,
opportunistic screening of patients consulted for unrelated reasons, opportunistic
screening of patients admitted for heart attack, and systematic screening of first degree
relatives of diagnosed patients.
The authors used a simulated population of those aged 15-64 in England and
Wales taking effectiveness data from a systematic literature review and authors‟
assumptions. They found that the tracing of family members would be the most cost-
effective strategy and universal population screening the least cost-effective. The authors
also found that the earlier in a lifetime the diagnosis is made, the more cost-effective the
screening strategy becomes in identifying cases. Also, as the cost of drugs (statins) falls,
all the strategies will become more cost-effective.
None of the studies reviewed were of pharmacogenomic technologies, such as
combinations of genetic test plus targeted medication. Within this subject area, there are
more clinical and theoretical articles available than cost-effectiveness or cost-benefit
studies of particular drugs or vaccines. Danzon and Towse  and Veenstra and
colleagues  produce interesting frameworks for the analysis of pharmacogenetic
interventions, but the methods they describe are not necessarily unique to the field of
From this literature search and review, it is evident that there is little work yet
available for health policy makers on which to base decisions. The bibliography we have
collected is available via the Cambridge Genetics Knowledge Park website
(http://www.cmgp.org.uk/jjdb/index.html). It shows that several hundred papers have
been published in the last 20 years. However, the quality and robustness of much of the
work is weak.
This review used very specific search terms and limits that could have missed data
that is available on the databases searched. This could be why some diseases commonly
tested for (such as Phenylketonuria (PKU)) did not appear in the final 37 studies. No
hand searching was done of journals and therefore selection bias (of those journals
available online) could have affected the study. Limiting the language could also have an
effect on the number of studies found. Further analysis of non-english publications
should be carried out.
1.Jarrett J., Mugford M. Genetic Health Technology and Economic Evaluation.
Journal of Applied Health Economics and Policy. IN PRESS. 2006.
2.Raven, Ann. Health Economics and Genetics Literature. Public Health Genetics
Unit. Cambridge, UK. April 2001.
3.Drummond MF, Jefferson TO. Guidelines for authors and peer reviewers of
economic submissions to the BMJ. The BMJ Economic Evaluation Working
Party. BMJ. 1996;313:275-83.
4.Tengs T O and Berry D A. The cost-effectiveness of testing for the BRCA1 and
BRCA2 breast-ovarian cancer susceptibility genes. Disease Management and
Clinical Outcomes. 1, 15-24. 2000.
5.Eccles DM, Englefield P, Soulby MA, Campbell IG. BRCA1 mutations in Southern
England. British Journal of Cancer. 1998;77(12):2199-203.
6.Grann VR, Whang W, Jacobson JS, Heitjan DF, Antman KH, Neugut AI. Benefits
and costs of screening Ashkenazi Jewish women for BRCA1 and BRCA2. J Clin
7.Heimdal K, Maehle L, Moller P. Costs and benefits of diagnosing familial breast
cancer. Dis Markers. 1999;15:167-73.
8.Brain K, Gray J, Norman P, France E, Anglim C, Barton G and colleagues.
Randomized trial of a specialist genetic assessment service for familial breast
cancer. J Natl Cancer Inst. 2000;92:1345-51.
9.Brown ML, Kessler LG. The use of gene tests to detect hereditary predisposition to
cancer: economic considerations. J Natl Cancer Inst. 1995;87:1131-36.
10. Reyes CM, Allen BA, Terdiman JP, Wilson LS. Comparison of selection
strategies for genetic testing of patients with hereditary nonpolyposis colorectal
carcinoma: effectiveness and cost-effectiveness. Cancer. 2002;95:1848-56.
11. Ramsey SD, Burke W, Clarke L. An economic viewpoint on alternative strategies
for identifying persons with hereditary nonpolyposis colorectal cancer. Genet
12. Vasen HF, van BM, Buskens E, Kleibeuker JK, Taal BG, Griffioen G and
colleagues. A cost-effectiveness analysis of colorectal screening of hereditary
nonpolyposis colorectal carcinoma gene carriers. Cancer. 1998;82:1632-37.
13. Chikhaoui Y, Gelinas H, Joseph L, Lance JM. Cost-minimization analysis of
genetic testing versus clinical screening of at-risk relatives for familial
adenomatous polyposis. Int J Technol Assess Health Care. 2002;18:67-80.
14. Murray J, Cuckle H, Taylor G, Littlewood J, Hewison J. Screening for cystic
fibrosis. Health Technol Assess. 1999;3:i-104.
15. Cuckle HS, Richardson GA, Sheldon TA, Quirke P. Cost-effectiveness of
antenatal screening for cystic fibrosis. BMJ. 1995;311:1460-1463.
16. Rowley PT, Loader S, Kaplan RM. Prenatal screening for cystic fibrosis carriers:
an economic evaluation. Am J Hum Genet. 1998;63:1160-1174.
17. Wildhagen MF, ten Kate LP, Habbema JD. Screening for cystic fibrosis and its
evaluation. Br Med Bull. 1998;54:857-75.
18. Nielsen R, Gyrd-Hansen D. Prenatal screening for cystic fibrosis: an economic
analysis. Health Econ. 2002;11:285-99.
19. OECD. PPPs for GDP. Historical Series. http:/www.oecd.org/std/ppp/.
20. DeVore GR, Romero R. Combined use of genetic sonography and maternal serum
triple-marker screening: an effective method for increasing the detection of
trisomy 21 in women younger than 35 years. J Ultrasound Med. 2001;20:645-54.
21. DeVore GR, Romero R. Genetic sonography: a cost-effective method for
evaluating women 35 years and older who decline genetic amniocentesis. J
Ultrasound Med. 2002;21:5-13.
22. Vintzileos AM, Ananth CV, Fisher AJ, Smulian JC, Day-Salvatore D, Beazoglou
T and colleagues. An economic evaluation of second-trimester genetic
ultrasonography for prenatal detection of down syndrome. Am J Obstet Gynecol.
23. Evans MI, Chik L, O'Brien JE, Chin B, Dvorin E, Ayoub M and colleagues.
MOMs (multiples of the median) and DADs (discriminant aneuploidy detection):
improved specificity and cost-effectiveness of biochemical screening for
aneuploidy with DADs. Am J Obstet Gynecol. 1995;172:1138-47.
24. Vintzileos AM, Ananth CV, Smulian JC, Day-Salvatore DL, Beazoglou T,
Knuppel RA. Cost-benefit analysis of prenatal diagnosis for Down syndrome
using the British or the American approach. Obstet Gynecol. 2000;95:577-83.
25. Adams PC, Valberg LS. Screening blood donors for hereditary hemochromatosis:
decision analysis model comparing genotyping to phenotyping. Am J
26. El-Serag HB, Inadomi JM, Kowdley KV. Screening for hereditary
hemochromatosis in siblings and children of affected patients. A cost-effectiveness
analysis. Ann Intern Med. 2000;132:261-69.
27. Marks D, Wonderling D, Thorogood M, Lambert H, Humphries SE, Neil HA.
Screening for hypercholesterolaemia versus case finding for familial
hypercholesterolaemia: a systematic review and cost-effectiveness analysis. Health
Technol Assess. 2000;4:1-123.
28. Danzon P, Towse A. The economics of gene therapy and of pharmacogenetics.
Value Health. 2002;5:5-13.
29. Veenstra DL, Higashi MK, Phillips KA. Assessing the cost-effectiveness of
pharmacogenomics. AAPS PharmSci. 2000;2:E29.