Page 162 - Hospital Authority Convention 2018

Masterclasses
HOSPITAL AUTHORITY CONVENTION 2018

M9.1 Clinical Genetics and Genomics – Application and Beyond 09:00 Room 221

Cost-effectiveness Analysis: Next Generation Sequencing versus Conventional Technologies
Wong KF
Department of Pathology, Queen Elizabeth Hospital, Hong Kong
The advent of next generation sequencing (NGS) or massively parallel sequencing technology enables us to interrogate
the whole genome within a short period of time. It also allows prompt diagnosis of rare inherited diseases and rapid
implementation of targeted therapy for cancers. It is now generally accepted that NGS can be used as a stand-alone test as
the use of orthogonal validation assay (e.g. Sanger sequencing) as a reference may not be necessary because of the higher
sensitivity and specificity of NGS. Still, it is important to examine the cost-effectiveness of such new technology before health
policy makers can decide on how one should allocate limited healthcare resources to such emerging and ever-increasing
demand for genomic test.

Cost-effectiveness can be defined by the mutation detection rate and how this will lead to a change in patient management
such as the targeted therapy for cancer. It has been estimated that over 80% of sequenced cancer patients harboured at
least 1 mutation, and 37% of them proceeded to receive therapy matching their genetic profile. The limiting factor is thus
the availability of gene therapy for that particular disease based on patient’s genomic information. It is noteworthy that the
cost of treatment is often much higher than the cost of doing the test and thus may have an impact on the cost-effectiveness
analysis. This may not hold true if NGS is used as a screening test for inherited diseases as the downstream cost is much
lower.

NGS is an effective test for defining clinically actionable mutations in patients with poorly understood clinical disorders, rare
inherited diseases and also in patients with cancers. It is, however, sometimes necessary to provide a multitude of tests,
including standard karyotyping, chromosomal microarray and NGS, in order to end the diagnostic odyssey for both patients
and clinicians.

M9.2 Clinical Genetics and Genomics – Application and Beyond 09:00 Room 221

Genetics and Genomics beyond Rare Diseases – The Future is Now
Chiu R
Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong

Diseases caused by genetic or genomic abnormalities were once managed by rare individuals with highly specialised medical
Tuesday, 8 May 2018 syndrome and toxic epidermal necrolysis could be mitigated by avoiding carbamazepine prescription in Asian individuals with
expertise. With the rapid expansion in knowledge in human genomics and the availability of powerful investigational tools, the
use of genetic and genomic tests are now infiltrating many branches of medicine. For example, the risks of Steven-Johnson
HLA-B*1502 allele. Warfarin doses could be titrated according to the person’s CYP2C9 and VKORC1 genotypes. Tyrosine
kinase inhibitors are the first line drugs for patients with non-small cell lung cancer harbouring sensitising epidermal growth
factor receptor mutations. Maternal blood DNA analysis allows for sensitive and specific, yet non-invasive, screening of fetal
chromosomal aneuploidies. Non-invasive DNA-based screening of fetal single gene diseases which are individually rare but
relatively common collectively, is now scientifically feasible and provides an opportunity for in utero or neonatal therapy.
Circulating tumour-derived DNA testing has been shown in a prospective study to be effective in the detection of early
nasopharyngeal carcinoma among asymptomatic community participants, with a demonstrable reduction in mortality. These
are just some of the examples whereby DNA testing on relatively large target populations has demonstrable clinical benefits.
Evidently, the incorporation of genetic and genomic information in medical care, aka. genomic medicine, is becoming a daily
routine in many areas of medical practice now. How may we, as healthcare professionals, better equip ourselves to embrace
this new paradigm?
(Supported by the Research Grants Council of the Hong Kong SAR Government under the Theme-based research scheme
(T12-401/16-W) and (T12-403/15-N)).

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