Transcript 06_Opthalmology India Advantage

Frankfurt
Bangalore
Ophthalmology Clinical
Research:
The India Advantage
Points of discussion
SN
Contents
1
Ophthalmic market in India
2
Ophthalmic diseases – clinical scenario in India
3
The Indian clinical trial space:
4
Summary & conclusions
1.
2.
3.
4.
5.
6.
7.
8.
1.
2.
3.
4.
5.
6.
Corneal transplantation
DME
Glaucoma
Refractive errors
ARMD
Cataract
Uveitis
Human resource needs
Regulatory/Ethics Committee
Institutional infrastructure
Ongoing trials in India
Clinical Research Infrastructure
Key Enrollment Indicators
Cost assumptions
2
Ophthalmic market
The market in India
3
Ophthalmology market: India
Ophthalmology market in India is at the forefront of a new
revolution
– Out of the seven Joint Commission International (JCI)
accredited hospitals in India, one is an eye hospital.
– Recently, an eye hospital from South launched its first
Initial Public Offering (IPO) which was fully subscribed
– Ophthalmology in India has evolved to be one of the most
sought after destinations, Under health tourism.
– Technology boom: Newer diagnostic modalities & high tech
equipment have enabled ophthalmologists
http://www.modernmedicare.in/article/Evolving-Ophthalmology/page1.html
4
Ophthalmology market: India
– New generation of informed patients
– Indian ophthalmology sector is well supported by a number
of accomplished eye care centers.
– Strong network of tertiary care institutes both in public and
private sectors has proved to be India’s strength in this
segment
– Refractive treatments are gaining popularity, both among
the public as well as among ophthalmologists.
5
Ophthalmic Device Market: India
• The ophthalmic medical device sector can be organized into
three major segments
– Diagnostics
– Cataract surgery products, including intraocular lenses,
viscoelastics, & phacoemulsification systems
– Refractive surgery products, including excimer and
femtosecond lasers, microkeratomes, and usage-based
procedure cards.
• In addition to devices, the ophthalmic market includes
pharmaceuticals and eye-care products such as contact
lenses and solutions.
6
Ophthalmic Device Market
 The worldwide ophthalmic products market exceeds $22 billion
& is growing at >10% per year.
 Not counting consumer eye-care products, the ophthalmic
products market reached an estimated $17 billion in 2006.
 Ophthalmic device market in India remains fairly fragmented
 Multinational firms have immense presence in some segments
 Some of the key players in this segment are Advanced
Opthalmic Imaging System, consolidated Products Corp. Pvt.
Ltd., Bausch & Lomb, Carl Zeiss, J&J vision care. Appasamy
Associates, Mehra Eyetech Pvt. Ltd., Toshbro Medicals,
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Ophthalmic Diseases
Clinical Scenario in India
8
Corneal transplantation in India
 Corneal transplantation, also known as corneal grafting or
penetrating keratoplasty
 According to Indian council of Medical Research (ICMR)
study on blindness, about 25% of the total blind in India
are blind due to corneal blindness
 The number of Corneal Blinds in India are about 4.60
Million
 In India, there is no dearth of knowledge, skills and
resources to create a world class eye banking and corneal
transplantation network
Corneal transplantation:
Potential centers in India*
Centre
No of Corneal
transplantation /year
L V Prasad Eye Institute Hyderabad
>600
Shankara Nethralya Chennai
>500
RP Centre of Ophthalmic Sciences New Delhi
>400
Clear Vision Mumbai
> 70
*Based on telephonic discussion with potential investigators
Diabetic Macular Edema (DME)
 Definition of DME: swelling of the retina in diabetes mellitus
due to leaking of fluid from blood vessels within the macula1
 Macular edema is common in diabetes with a lifetime risk of
10%1
 The condition is closely associated with the degree of diabetic
retinopathy
• Clinically Significant Macular Edema (CSME), as defined by the Early Treatment Diabetic
Retinopathy Study (ETDRS), includes any of the following findings2,3
– Retinal thickening within 500 µm of the center of the fovea
– Hard, yellow exudates within 500 µm of the center of the fovea with adjacent retinal thickening
– At least 1 disc area of retinal thickening, any part of which is within 1 disc diameter of the center of the fovea
Source: 1” Definition of Diabetic macular edema”, MedicineNet.com Website Accessed on May 12, 2009, 2“Macular Edema, Diabetic”, emedicine
Website Accessed on May 12, 2009, 3“International Clinical Classification of Diabetic Retinopathy, Severity of Diabetic Macular Edema, Detailed
Table”, International Council of Ophthalmology, October 2002
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DME Prevalence Estimates for 2009
Population of India1
(1,197M)
Diabetic patients2: 36.4M
Worksheet
CSME
(Based on
Study 1)
CSME
(Based on
Study 4)
2.18M (6% of diabetic
patients)
1.41M (3.9% of
diabetic patients)
Worksheet
• Assumption: type 1 diabetes constitutes a negligible
proportion of the total diabetics
• Assumption: the prevalence of DME in diabetic patients < 30
years of age is negligible*
• The prevalence of type 1 diabetes is 0.01%3
• Adjusting the prevalence rate of CSME to all age group (Study
4)
• Prevalence rate of CSME among diabetic patients (based on
the above assumption): 6% (Study 1)
• Prevalence of CSME in diabetic patients > 30years: 4.1%
• The above-mentioned prevalence rate was adjusted
considering the assumption and accounting for additional
prevalent patient pool to make up for all age group4
• Adjusted prevalence rate (all age group) is 3.9%
*Considering the fact that the mean age of patients with
DME has usually been > 50 years in many studies
Source: 1United Nations population Division Website Accessed on May 12, 2009, 2Sarah Wild et al (2004), “Global Prevalence of Diabetes”, Diabetes Care 2004;
Vol. 27:1047–1053 3Pushpa Krishna et al (2005), “Dyslipidemia in Type 1 Diabetes Mellitus in the Young”, International Journal of Diabetes in Developing
Countries 2005;Vo1 25 (4):110-12, 4Anil J Purty et al (2009), “Prevalence of Diagnosed Diabetes in an Urban Area of Puducherry, India: Time for preventive
action”, Int J Diab Dev Ctries 2009;29:6-11
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Prevalence – DME/CSME (1/2)
Author
Region
Patient segment
&n
Sunil’s Diabetes Care
n’ Research Centre
Pvt. Ltd. (DCRC)
Nagpur
Type 2 diabetic
patients (n=350)
Ramachandran
A et al2
Diabetes Research
Centre, Chennai
Type 1 diabetic
patients aged < or
=20 years at
diagnosis of
diabetes (n=617)
V Narendran et
al3
Aravind Medical
Research Foundation,
Aravind Eye Care
System, Madurai,
Tamilnadu (Study
done in Palakkad,
Kerala
Sunil Gupta and
Ajay Ambade1
Diabetic patients
> or = 50 years
(n=260)
Year
Prevalence in population
2004
CSME:
• 6% of type 2 diabetic patients
• 17.9% of DR patients (type 2
diabetes)
• 21.5% of insulin dependent type 2
diabetic patients
• 12.96% of type 2 diabetic patients on
oral anti-diabetic drugs
• 14.3% of type 2 diabetic patients with
albuminuria
2000
CMSE:
• 1.8% of type 1 diabetic patients aged
< or = 20 years
• 13.3% of DR patients (type 1 diabetic
patients aged < or = 20 years)
2002
CMSE
• 7.7% of diabetic patients (> or = 50
years)
• 29.4% of DR patients (> or = 50
years)
Source: 1Sunil Gupta (2004), ” Prevalence of Diabetic Retinopathy and Influencing Factors Amongst Type 2 Diabetics from Central India”, Int. J. Diab. Dev.
Countries 2004; Vol. 24:75-78, 2Ramachandran A et al (2000), “Vascular Complications in Young Asian Indian Patients with Type 1 Diabetes Mellitus”, Diabetes
Res Clin Pract. 2000 Apr;48(1):51-6, 3V Narendran et al (2002), “Diabetic retinopathy among self reported diabetics in southern India: a population based
assessment”, Br J Ophthalmol 2002;86:1014–1018
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DME – Treatment Flow (PMR, India)
N=2
DME patients constitute 90% of the Macular Edema patients
Clinically Significant Macular
Edema (CSME) - 40%
Diabetic Macular Edema
(DME) – 100%
Clinically Insignificant
Macular Edema – 60%
Focal Macular Edema (FME) –
60%
Diffuse Macular Edema
(DiME) – 40%
Focal CSME – 40% of FME
Diffuse CSME – 40% of DiME
First-line of therapy –
100%
CSME
Treatment
• Irrespective of severity, CSME patients would
be administered treatment
• Sometimes, physicians may also treat clinically
insignificant DME (Intravitreal anit-VEGF and
laser treatment on deterioration)
Second-line of therapy –
25%-30%
Third-line of therapy – 5%
Focal Macular Edema
Focal Macular Edema
• Intravitreal steroids and
anti-VEGF (AVASTIN)
Focal Macular Edema
• Focal laser treatment
• Focal laser treatment
• Vitrectomy
Diffuse Macular Edema
Diffuse Macular Edema
Diffuse Macular Edema
• Grid laser treatment
• Intravitreal steroidsand
anti-VEGF (AVASTIN)
• Vitrectomy
• Grid laser treatment
Source: KOL interviews
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Glaucoma
 Glaucoma represents a heterogeneous group of optic
neuropathies and is estimated to affect 12 million Indians; it
causes 12.8 per cent of the total blindness in the country and
is considered to be the third most common cause of blindness
in India
 An Asian survey presented at the World Ophthalmology
Congress in Hong Kong in July 2008 revealed that between
2010 and 2020, India will be the world’s glaucoma capital.
 Primary angle-closure glaucoma (PACG) is a major form of
glaucoma in Asian countries. According to an Indian hospitalbased data, PACG appears to be as prevalent as primary
open-angle glaucoma (POAG), accounting for 45- 55% of
primary glaucoma cases.
Henson DB, Thampy R. Preventing blindness from glaucoma. BMJ. 2005; 331 Suppl 7509:120-1
Chew PT, Aung T. Primary angle-closure glaucoma in Asia. Journal of Glaucoma 2001; 5 Suppl 1:S7-S8
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Glaucoma – treatment
 Since the disease is not curable early detection and
prevention are the key focus areas, however, surgery and
laser treatment do appear to be promising
 Treatment includes - glaucoma surgeries
– trabeculectomy - the procedure of choice particularly for
secondary glaucomas.
– Various new modalities - mini trab procedure ,non penetrating
filtering procedure, trans ciliary filtering’ surgery in 2004, ‘limbal
filtering’ surgery in 2006 using a fugo plasma blade.
– Newer glaucoma surgeries (non-penetrating) like deep
sclerectomy, viscocanalostomy and trabeculectomy ab-externo
have also shown promising results.
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Glaucoma treatment - latest procedures
– Cyclocryotherapy for ciliary body ablation helps reduce the
eye pressure and alleviate pain.
– Glaucoma implants have been used for patients who are
not responding to maximal medical therapy or are failed
glaucoma surgery or poor candidates for glaucoma
surgery.
– Selective Laser Trabeculoplasty (SLT)
– Ciliary body diode laser cycloablation
– Nd:YAG Laser peripheral iridotomy
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Refractive errors
 Refractive errors (myopia, hypermetropia, astigmatism,
presbyopia) result in an unfocussed image falling on the
retina.
 Uncorrected refractive errors, which affect persons of all ages
and ethnic groups, are the main cause of visual impairment.
 There are estimated to be 153 million people with visual
impairment due to uncorrected refractive errors, i.e.
presenting visual acuity < 6/18 in the better eye, excluding
presbyopia.
 Globally, uncorrected refractive errors are the main cause of
visual impairment in children aged 5–15 years. The
prevalence of myopia (short-sightedness) is increasing
dramatically among children, particularly in urban areas of
South-East Asia.
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Refractive vision correction
 The most frequently used options for correcting
refractive errors are:
– spectacles, the simplest, cheapest and most widely used
method;
– contact lenses, which are not suitable for all patients or
environments;
– corneal refractive surgery, which entails reshaping the cornea by
laser.
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Trends in refractive vision correction
 The path to refractive corrections for myopia, hyperopia,
presbiopia and astigmatism is pitted with technologically sound
techniques
 Broad range of options to treat each patient’s unique needs
–
–
–
–
LASIK, Laser-Assisted Sub-Epithelial Keratectomy (LASEK)
clear lens exchange (CLE),
phakic intraocular lenses (PIOL), and
conductive keratoplasty (CK)
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Age Related Macular Degeneration (ARMD)
 Age-related macular degeneration is the commonest cause of
blindness in industrialized countries.
 Age-related macular degeneration has two forms, ‘wet’ and
‘dry’. In most populations, the dry form is the more frequent,
but it is less likely to lead to severe bilateral visual loss.
 Age-related macular degeneration is responsible for 8.7% of
all blindness (3 million persons) due to eye diseases, ranging
from close to 0% in sub-Saharan Africa to 50% in
industrialized countries.
 The number affected is expected to double by the year 2020
as a result of the ageing of the world’s population.
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Upcoming trends in the treatment of ARMD
• Photodynamic therapy (trade name Visudyne) uses a nonthermal (or cold) laser with an intravenous light-sensitive drug
to seal and halt or slow the progression of abnormal retina
blood vessels.
• LASER photocoagulation is a procedure involving the
application of a hot laser to seal and halt or slow the
progression of abnormal blood vessels
• New anti-vascular endothelial growth factor agents are being
investigated, and more research is needed.
• Surgical translocation of the macula and submacular surgery
are indicated only for selected patients, as surgery requires
highly experienced vitreo-retinal surgeons, and the results are
not always favourable.
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Cataract
 The most recent estimates from WHO reveal that 47.8% of
global blindness is due to cataract
 South Asia region which includes India, 51% of blindness is due to
cataract
 Approximately, nine million Indians are blind from cataract with
another 1.8-3.8 million going blind from cataract every year.
 Ophthalmologists and programme planners have been able to
effectively increase cataract surgical output from a low of 1.2
million surgeries in 1992 to a high of 4.8 million surgeries in
2006 with intraocular lenses (IOLs) used in 90 per cent of
cases
Indian J Ophthalmol. 2008 Nov–Dec; 56(6): 489–494. “Current status of cataract blindness and Vision 2020: The right to sight initiative in
India”
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Reasons for decreasing in blindness prevalence
 25% decrease in blindness prevalence in India (WHO report)
 This could be due to the increased cataract surgeries in the
country
 Due to factors
– indigenous manufacturing of IOLs,
– equipment and supplies for cataract surgery,
– structured training programmes,
– infrastructure development and
– co-ordinated efforts by the Government and the
international NGOs
Murthy GV, Gupta SK, Bachani D, Jose R, John N. Current estimates of blindness in India. Br J Ophthalmol. 2005;89:257–60
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Uveitis and its Classification
•
Uveitis is a potentially blinding intraocular inflammation1
•
The inflammation can include iris, ciliary body, choroid, retina, optic nerve and vitreous 1
Uveitis2
Anterior Uveitis
Intermediate Uveitis
Posterior Uveitis
Pan Uveitis
► Location: Iris ,
ciliary body &
cornea
► Location:
Peripheral retina,
pars plana &
vitreous
► Location: Choroid
& Retina
► Location: anterior
chamber, vitreous,
and retina and/or
choroid
► Main Causes:
Idiopathic, HLAB27 association,
Trauma, Infection
► Main Causes:
Idiopathic,
Systemic
disorders like
sarcoidosis,
Multiple sclerosis
etc
► Main Causes:
Infections,
Systemic
disorders
► Main Causes:
Infections
• Common causes of Uveitis in a 2006-07 study in 475 patients at AIIMS Delhi:3
• 65% no definitive etiology
• Systemic disorders: Ankylosing spondilytis, TB, juvenile idiopathic arthritis and sarcoidosis
• Ocular disease: Ocular toxoplasmosis
• Other: Serpiogenous chorditis, Behcet’s disease, VKH syndrome etc
Sources: 1O.M. Durrani et al. “Uveitis: A Potentially Blinding Disease” Ophthalmologica 2004, 2Robert H Janigian Jr “Uveitis, Evaluation and
Treatment” emedicine November 2007, 3Dr. Subrata Mandal et al. “Prevalence and Clinico-Epidemiological Profile of Uveitic
Blindness” AIOC 2008 PROCEEDINGS
Uveitis – Treatment Flow (PMR, India)
N=2
Treated Uveitis
Infective
Steroid
(100%)
Non-infective
Anterior Uveitis
(44%)
Antibiotic
(15-20%)
Intermediate Uveitis
(16%)
Posterior Uveitis
(25%)
Pan Uveitis
(15%)
Observation (0-2%)
Acute (95%)
Topical
Steroid (90-98%)
Periocular
Steroid (5-10%)
Observation (0%)
Acute (40%)
Chronic (5%)
Topical
Steroid (100%)
Chronic (60%)
Acute (40%)
Chronic (60%)
Systemic
Steroid (20-25%)
Acute (20%)
Immunosuppressant
(2-5%)
Chronic (80%)
Cycloplegics
(80-90%)
Sources: KOL interviews & Secondary estimates
Periocular
Steroid (10-20%)
Systemic
Steroid (90-100%)
Acute (40%)
Chronic (60%)
Acute (50%)
Chronic (50%)
Immunosuppressant
(2-5%)
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Active Uveitis Prevalence Estimates for 2009
Indian population
1,197.2M
Base Case
Numbers in million
Prevalence of Active Uveitis, 0.37%
4.4M
Anterior Uveitis
1.92M
Downside case
Anterior Uveitis
0.99M
Upside case
Anterior Uveitis
3.65M
Intermediate Uveitis
0.71M
Posterior Uveitis
1.11M
Pan Uveitis
0.67M
Prevalence of Active Uveitis, 0.19%
2.2M
Intermediate Uveitis
0.36M
Posterior Uveitis
0.57M
Pan Uveitis
0.34M
Prevalence of Active Uveitis, 0.70%
8.38M
Intermediate Uveitis
1.35M
Posterior Uveitis
2.1M
Pan Uveitis
1.27M
Note: Weighted average distribution of the studies is considered for the estimation of subtype prevalence: Anterior Uveitis
44%, Intermediate Uveitis 16%, Posterior Uveitis 25% & Pan Uveitis 15%
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The Right to Sight in India
 India was the first country in the world to launch the National
Programme for Control of Blindness in 1976 with the goal of
reducing the prevalence of blindness.
 Of the total estimated 45 million blind persons in the world, 7
million are in India.
 Due to the large population base & increased life expectancy,
the no. of blind particularly due to age-related disorders like
cataract, is expected to increase
 Main causes of blindness in 50+ population are cataract
62.6%, refractive errors 19.7%, corneal blindness 0.9%,
glaucoma 5.8%, surgical complications 1.2%, posterior
segment disorders 4.7%, others 5.0%
http://www.who.int/blindness/Vision2020%20-report.pdf
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Vision 2020: Indian Scenario
• India is a signatory to the WHO resolution on Vision 2020:
The right to sight
• Launched jointly by WHO and the International Agency for the
Prevention of Blindness (IAPB) with an international
membership of NGOs, professional associations, eye care
institutions and corporations
• Envisions eliminating the main causes of avoidable blindness
by the year 2020
• Programmes will be based on three core strategies
– Disease control,
– Human resource development and
– Infrastructure and technology
incorporating the principles of primary healthcare
http://www.aios.org/cmefiles/CME_9.pdf
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Human Resource needs: India
Vision 2020: CME series 9
There are >15000 trained ophthalmologists in India
30
Clinical Profile of Institutions in India
Based on survey with 128 medical institutions offering training
31
The Clinical Trial Space
Scenario in India
32
Growth in clinical research
• Outsourced Clinical Drug Trials increasing in number and
complexity
• 2001 – 2005 : 178% growth in number
• Varied motivators
•
•
•
•
•
•
Rapid patient accrual
Medical expertise
Regulatory, Ethical & Industrial infrastructure
GCP mandated by legislation
Evolving clinical research regulatory framework
Product patents
33
Regulatory and Ethics Committee
 New guidelines released for “requirements for the
manufacture, import and sale of medical devices” in 2009 will
pave way growth in this area.
 Recent examples of approving the products for marketing
based on the Global CT data has created an interest in global
players. However, a clear justification & data supporting MAA
and a substantial sample of Indian subjects have to be
enrolled in the Global CTs.
 Regulatory timelines for CT approvals are 45 days
 ECs timelines range from 15 days to 2 months
 EC working procedures defined by local regulatory framework
(Schedule Y)
34
Regulatory Environment: General classification
CLASS
RISK LEVEL
DEVICE EXAMPLES
A
Low Risk
Thermometers / tongue depressors
B
Low-moderate
Risk
Hypodermic Needles / suction equipment
C
Moderate-high
Risk
Lung ventilator / bone fixation plate
D
High Risk
Heart valves /implantable defibrillator
The Figure shows increasing levels of regulatory
requirements as the device risk class increases
35
Institutional infrastructure
• Specialized institutions in the ophthalmology segment (eg.
Sankara Nethralay- Chennai, LVPEI – Hyderabad, Aravind –
Madurai)
• Institutional ethics committee complying with ICH GCP &
Schedule Y requirements
• Availability of standard equipment (Computer lensometer,
Contrasting sensitivity testing, Ultrascan, Computerized
Microscopy, Fundus camera, Optical Coherence
Tomography, Slit lamps)
• Highly qualified & experienced clinicians
• Availability of trained technicians – (Special training schools
provide a steady availability of manpower)
• Many technicians certified for BCVA, FP, OCT
36
Potential sites for clinical studies in India
•
Sankara Nethralaya, Chennai
•
Aravind Eye Hospital, Madurai, Pondicherry & Tirunelveli
•
LV Prasad Eye Institute, Hyderabad
•
Regional Institute of Ophthalmology, Chennai
•
AIIMS, New Delhi
•
Lotus Eye Hospital, Coimbatore
•
Shroff Eye Hospital, Mumbai
•
Aditya Govt Hospital, Mumbai
•
•
Mahaveer Jain Hospital Bangalore
Narayana Nethralaya, Bangalore
•
Clear vision eye centre, Mumbai
•
Dept of Ophthalmology, Sir Ganga Ram Hospital, New Delhi
•
Dept of Ophthalmology, St. John’s Hospital, Bangalore
•
Dept of Ophthalmology, Nair hospital, Mumbai
37
Currently ongoing trials in India
•
•
•
•
•
•
Glaucoma (5)
Macular edema (2)
Refractory error (2)
Cataract (1)
Macular degeneration (1)
Eye infections
* Based on current CT registry, India
India participant in major global phase III trials
38
Ecron Acunova Experience in Ophthalmic studies
Sl
No.
Indication
Phase of
study
Sample size
(Pts)
No of sites
1
Allergic conjunctivitis
III
120
6
2
Cataract
III
75
6
3
Glaucoma
III
120
10
4
Glaucoma
III
30
5
5
Post Cataract
Surgery
III
150
6
6
Cataract
III
210
6
Trials completed within planned timelines
39
Clinical research infrastructure
• Availability of skilled Clinical Research Organizations
including full service capabilities
• Trained & experienced manpower :
– Educational background – Medical, Paramedical, Life Sciences
(graduate, postgraduate & Ph.D)
– Experience ranging from 2-10 years
• Range of services offered include:
–
–
–
–
–
–
Medical writing & Biostatistics
Clinical monitoring & Project Management
Data Management & Biometrics
Clinical supplies management
Central Laboratories
Archival facilities
40
Key enrollment indicators
• Average time to reach critical milestones from contract sign
off (Based on a phase III study completed at EA):
– 100% sites initiated : 3.5 months
– First patient enrolled : 4 months
– Last patient enrolled : 6 months
(Recruitment period : Actual/Planned – 8 weeks /12 weeks)
• All ophthalmology studies at EA completed enrollment within
planned timelines
41
Cost assumptions
• Competitive service costs
• Major variable cost – site cost
SAMPLE INVESTIGATOR SITE COST STRUCTURE
Per visit
Principal Investigator (per patient / visit)
USD 60 -150
Co-Investigator (per patient / visit)
USD 40 - 80
Per month
Study coordinator (monthly)
USD 200 -300
Ethics committee (One time payment)
USD 200 - 400
3 Visits
USD 180 - 450
USD 120 - 320
6 months
USD 1200 - 1,800
Other costs
Institutional fee (20% of overall budget)
Clinical & Lab investigations (based on
protocol)
42
Summary and Conclusions
 Indian ophthalmology industry is showing significant promise
 In the coming years, the ophthalmology market will continue to
support a healthy mix of both device and pharmaceutical therapies,
as well as combination products that blur the line between the two
industries.
 More than 15000 trained ophthalmologists
 Large pool of qualified, experienced, English speaking investigators
and support staff
 Language used for regulatory submissions & clinical research is
English
 Data generated in Global CTs can be used for Indian NDAs
provided sufficient no. of subjects from India is included in the study
 New device guidelines is expected to pave way for a significant
increase in CT and device market share
43