1. Early assessment of new technologies
The case of whole exome sequencing in complex
pediatric neurology Kirsten van Nimwegen, MSc
Janneke Grutters, Gert Jan van der Wilt
Department for Health Evidence, Radboud umc
HTAi Annual Meeting,
June 17, 2014, Washington DC , USA
kirsten.vannimwegen@radboudumc.nl

2. Early health technology assessment
• Growing need for early evaluation
• Early HTA might enhance innovation in health care
• Potentially promising developments in the field of next-generation
sequencing techniques, such as whole exome sequencing (WES)
• Complex disease of genetic origin

3. Objective
• To determine the value of the early assessment of innovative technologies,
examplified by the potential use of WES as a novel genetic test in the
diagnostic trajectory of complex pediatric neurology

4. Methods (I)
• Evaluation of the current diagnostic trajectory
• Population: Children (<18y) with complex pediatric neurologic disorders
of suspected genetic origin
• Outcomes: Health care utilization and diagnostic yield
• Perspective: Healthcare system
• Evaluation of the value of WES in this trajectory regarding costs:
• Scenario analysis, based on how WES may be used in clinical practice

5. Methods (II) Scenario analysis
Scenario
1 WES as an add-on test
2 WES replaces only the genetic tests currently used
3 WES replaces all genetic and repeated* diagnostic tests
4 WES replaces most genetic and some (repeated* and burdensome**) other
diagnostic tests, and a certain amount of physician visits***
5 WES replaces all diagnostic tests & all but 2 physician visits
* MRI, X-ray and EEG
** Lumbar punctures and biopsies
*** Substitution of 50% of the physician visits
• Costs WES: €3,600 ($4,884)

6. Results Current diagnostic trajectory
• n = 50
• Mean duration: 40 months
• Diagnostic yield: 6%
• Mean costs €12.475 ($16,925)
Category Mean
quantity
Mean costs (€ )
(2.5 – 97.5 percentile)
Percentage of
total costs
Physician consultations 32.62 3,112 (2,408 – 3,885) 24.9%
Imaging tests 4.46 829 (644- 1,031) 6.6%
Neurophysiology tests 2.48 424 (318 – 549) 3.4%
Genetic tests 7.56 5,321 (4,596 – 6,167) 42.7%
Other diagnostics 15.08 2,812 (2,346 – 3,315) 22.5%
Total 12,475 (10,774 – 14,404)

7. Results Scenario analysis
+3,600
-1,721 -2,113 -2,812 -8,601
Current
practice

8. Discussion
• Our scenario analysis shows that all scenario’s of implementing WES,
except using it as an add-on test, will reduce health care expenditure
• High uncertainty around eventual costs and effects
• Technologies under development
• Negative result might reject promising innovations and stifle innovation
• Positive result might accelerate implementation, enhancing innovation
• In the case of WES
• How will it develop?
• How to interpret genetic diagnoses
• Downstream costs due to additional testing

9. Take-home message
• By showing a range of possible scenario’s to use whole exome sequencing,
and their consequences, we can explore the potential value of this
technology and how to implement it into clinical practice

10. Take-home message
• By showing a range of possible scenario’s to use whole exome sequencing,
and their consequences, we can explore the potential value of this
technology and how to implement it into clinical practice