Outline of Presentation What is Clinical Research? Children's Health

Dr. Toh Teck Hock
Paediatrician, Department of Paediatrics
cum Head, Clinical Research Centre,
Sibu Hospital, Sibu, Sarawak
with input from Dr. Wong See Chang,
Head of Paediatric Department, Sibu Hospital
What is Clinical Research?
� Clinical research covers various types of studies
focused on human being, including new drug or
medical device development, multi-center clinical
trials, translational researches using biological
materials, and epidemiological studies.
� Clinical researches are directed by physicians,
researchers and other healthcare professionals.
� Clinical research is about up-to-date evidencebased
medical practices.
From clinician to “investigator scientist”:
� Started by doing clinical audit during housemanship
in West Cumberland Hospital, Whitehaven, UK
� Outstanding Audit - First Year Glycated Hb A1c in
Children with IDDM - Clinical Effectiveness
Conference, University Hospitals of Leicester,
United Kingdom
� Moving to studies, writing papers .... United
Kingdom and Singapore.
Outline of Presentation
� Discuss the importance of Clinical Research
in Children Health
� Explore the common topics of clinical
research in children health
� Discuss some local clinical research and
their impacts on children health in Sarawak
� Hidden Agenda: make the audience
interested in / excited about doing clinical
research
Children’s Health
� Not just absence of illnesses / diseases
� Covers key issues, including:
� health promotion
� surveillance and screening
� children's responses to illnesses / treatment
� cost-effectiveness
� vulnerable populations
� health services
� community health (development & learning, lifestyle
environment, etc.)
� Etc…….
Re-infected by the Clinical Research Flu
� Then...... back to Malaysia � “clinical worker” Prof. Frank Oberklaid: “spend time on Clinical
Research, it’s important and interesting”.

Why Research in Children’s Health
� Early years of children's lives and significant impact on
physical, behavioural & social development later in life.
� Many childhood conditions & problems are preventable or
can be improved if recognised and managed early.
� Best results = professionals work in close partnership
with parents who are supported & empowered to make the
best choices for their children.
� Translate up-to-date research and evidence (those shown
to be effective and appropriate) into policy formulation at
all levels (children / families, to school and community /
country).
Ref: http://www.rch.org.au/ccch/index.cfm?doc_id=10694
Unique features of Clinical Research in Children’s Health*
� Often involve multi-disciplinary team – various methodological
approaches
� Often aims to study full spectrum of child development &
behaviour – reliability & validity
� Often addresses more abstract issues – e.g. community support,
adjustment to illness (validated measures not available)
� Ecological perspective (i.e. socio-cultural influences on child
development and behaviour) – difficulty to measure, report
accurately, and interpret/explain
� Often relies on parent report – influenced by parents’ own
perception of state
� Advocacy issues (protecting interest of the children)
� Ethical issues (confidentiality, disclosure, ability to consent, use
of placebo)
*Research Foundation, Methods & Issues in Developmental-Behavioural Paediatrics: D
Schonfield, B Dreyer, Developmental-Behvaioural Paediatrics by Wolraich et al, 2008
Main research themes in CCCH, RCH:
� Development, behaviour and mental health
� Hearing
� Language, learning and literacy
� Obesity & Healthy Weight
� Safety promotion and injury prevention
� Children with additional needs
*New Millennium Morbidities in Paediatrics
What works? The need of evidence and the
“best-buy” concept)
� Like any other health care intervention, health
promotion activities can do harm as well as good (e.g.
inaccurate/incorrect information offered, poor screening test for a
variety of reasons, health information causing anxiety/guilt, etc.)
� Ethical imperative to ensure that child health
promotion activities are subjected to as robust an
evaluation as any other health care intervention.
� Research base in health promotion takes time to
develop and absence of evidence of effect is not the
same as evidence of absence of effect.
Ref: D Hall & D Elliman: Health for All Children, 4 th ed. 2003, p 22-25
Common / Important
Children’s Health
Research Topics

Child and adolescent health and development
topics in WHO
�Development: The future of human societies depends on
children being able to achieve their optimal physical growth &
psychological development.
�Rights: Life, survival, maximum development, access to health
and access to health services are not just basic needs of
children and adolescents but are also fundamental human
rights.
�Prevention & care of illness:
� Newborns, infants and children
� IMCI (Integrated Management of Childhood Illness)
� Adolescents
� Nutrition (breastfeeding, complementary feeding, malnutrition,
feeding in special circumstances such as HIV and etc.)
Developmental-Behavioural Referrals in LKHMCC,
Department of Paediatrics, Sibu Hospital (1998 –2010)
2010: 66% of Department’s
Clinic New Case Workload
Children with Learning Difficulty?
�Who are they?
�What are their abilities?
�Any associated problems?
In Malaysia …
� Probably Similar
� MOH Paediatricians Meeting 2011 on
obesity
� Vaccination, child abuse, safety and
injuries prevention
� (Acute and chronic paediatric illnesses)
� Different areas may have some
differences and focus
Increasing numbers of school children for
medical assessment referred in 2010:
� 94 primary one students referred for learning
difficulty in LKHMCC
� NKRA: Setiap kanak-kanak
menguasai kemahiran asas
literasi & numerasi selepas
mengikuti 3 tahun pendidikan
rendah pada akhir tahun
2012.
http://www.moe.gov.my/index.php?id=244&lang=my
Slow Learner vs. Learning Difficulty:
What’s in the names? – KPM / MOE
Ciri-ciri:
�Pencapaian pelajaran / akedemik berbeza.
�Pendiam / tidak aktif / banyak cakap.
�Sukar menerima arahan.
�Tidak dapat berkomunikasi seperti kanak-kanak biasa.
�Menyebut huruf 2 yg tidak tepat/salah, bertukar-tukar.
�Meninggalkan huruf, sukukata & perkataan ketika
membaca dan menulis.
�Tulisan yang terlalu buruk / sukar dibaca.
�Kekerapan kesalahan dalam ejaan, tanda bacaan.
�Tanpa ketetapan / menaik dan menurun
�Huruf terbalik / urutan dan arah yang salah
�Tanpa ketetapan & ketentuan - jarak huruf / perkataan.
�Saiz yg tak seragam/mencampuradukkan saiz–.
�Idea tak berkembangan & penyusunan idea tak teratur.
�Perbendaharaan kata terhad & tatabahasa yg tak tepat.
Punca:
•Baka
•Tersekat pengalaman
•Intelek yang rendah
•Masalah emosi
•Kekecewaan
•Rasa rendah diri
•Kemantangan yang lambat
•Lemah daya ingatan
•Mudah terganggu tumpuan
•Kurang rangsangan
•Faktor-faktor kesihatan
•Persekitaran
•Amalan makanan
•Kesan semasa mengandung
•Penyakit semasa
pembesaran selepas lahir.
•Ubat semasa mengandung.
•Kemalangan.
•Sosio-ekonomi.
Unit Bermasalah Pembelajaran, Sektor Kurikulum, Bhg. Pengurusan Sekolah, Jabatan Pendidikan Khas, KPM
SK Senai, Johor (http://www.sksenai.com/blogs/index.php/2008/07/23/lembam-slow-learner?blog=6)

Who’re these children with Learning Difficulties?
Diagnosis (n = 93) –
Male (n = 58) Female (n = 35) Total, p=0.24
(n = 93)
Borderline ID 23 (39.7%) 12 (34.3%) 35 (37.6%)
Mild ID 11 (19.0%) 7 (20.0%) 18 (19.4%)
SLD / Dyslexia 6 (10.3%) 4 (11.4%) 10 (10.8%)
ADHD 10 (17.2%) 1 (2.9%) 11 (11.8%)
ASD 3 (5.2%) 2 (5.7%) 5 (5.4%)
Severe Lang. Dis. - 3 (8.6%) 3 (3.2%)
Bilateral SNHL 1 (1.7%) 1 (2.9%) 2 (2.2%)
Low Vision - 1 (2.9%) 1 (1.1%)
Moderate ID 1 (1.7%) - 1 (1.1%)
Incomplete 1* (1.7%) 2 † (5.7%) 3 (3.2%)
Normal Cognition
(no specific cause)
2 (3.4%) 2 (5.7%) 4 (4.3%)
*probable borderline intellectual disability; † probable dyslexia / language disorder
Among those with ADHD, Borderline ID,
Mild ID and SLD: - The Mental Health
Borderline / Significant Concerns
Internalizing Externalizing
Parental Report 25-50% 27-60 + %
Teacher Report 42-70 + % 17-70 + %
Other local researches that
had / have potential to help
improving children’s health
How “smart” ‘re they? (Naglieri’s Non-verbal Ability Test)
Scores Percentile Male
NNAT percentile (n =53)
Female
(n =32)
Total
(n = 85)
< 70 < 2 pc (ID) 5 (9.4%) 3 (9.4%) 8 (9.4%)
71 – 80
81 – 89
90 – 110
111- 119
3 – 9 pc
(Borderline)
10 – 24 pc
(Low Average)
25 – 75 pc
(Average)
76 – 90 pc
(High Average)
11
(20.8%)
25
(47.2%)
13 (40.6%)
5 (15.6%)
8 (15.1%) 9 (28.1%)
24
(28.2%)
30
(35.3%)
17
(20.0%)
4 (7.5%) 2 (6.3%) 6 (7.1%)
> 120 > 91 pc - - -
* 9 of original 94 children studied (9.6%) did not do the NNAT because
“refused”, “unable to understand”, “did not concentrate”.
If results replicated nationwide and show
similar results, can advise / suggest:
� MOH on training purposes (recognising the
differences) and guiding the follow up / clinic
consultation
� MOE on planning of resources and teachers –
diagnosis are heterogenous and different /
normal ability
� Society – children with learning difficulty has
associated co-morbidities and need special
attention
Vaccination & Children Health
� Newer Vaccines:
� Chicken pox, Rotavirus, H1N1, Pneumococcal, Anticervical
cancer, Hepatitis …
� What is our country’s disease burden and types of
strain
� Which vaccines – can our budget take all
� Current Vaccination Schedule:
� Effectiveness and uptake
� Safety profile
� Cold chain practices

Research Partnership leading to introduction
of JE vaccination schedule in Sarawak, 2001
– Sibu Hospital, UNIMAS, Uni. of Liverpool, Sarawak State
Health Department with the support of MOH Malaysia
� SC Wong, MH Ooi, AR Abdullah, SY Wong, S Krishnan, PH Tio, PC Pek, BF
Lai, A Mohan, J Muhi, A Kiyu, MT Arif, MJ Cardosa. A Decade of
Japanese Encephalitis Surveillance in Sarawak: 1997 TO 2006.
Tropical Medicine and International Health; Volume 13 No 1 PP 52-55
January 2008.
� MH Ooi, P Lewthawaite, BF Lai, A Mohan, D Clear, L Lim, S Krishnan, T
Preston, CH Chieng, PH Tio, SC Wong, MJ Cardosa and T Soloman. The
Epidemiology, Clinical Features and Long Term Prognosis of Japanese
Encephalitis in Central Sarawak, Malaysia 1997 to 2005, Clinical
Infectious Diseases 15 Aug 2008:47.
Solving the mysterious HFMD - towards better
children’s health.
– Research Partnership among Sibu Hospital, UNIMAS
& University of Liverpool
- with support of Sarawak State Health Department
and MOH Malaysia
� M J Cardosa, S Krishnan, PH Tio, D Perera, SC Wong. Isolation of Subgenus B
Adenovirus during a fatal outbreak of enterovirus 71-associated hand,
foot, and mouth disease in Sibu, Sarawak. The Lancet, Vol 354, Sep 18, 1999.
� MH Ooi, SC Wong, Y Podin, W Akin, S del Sel, A Mohan, CH Chieng, D Perera, D
Clear, D Wong, E Blake, MJ Cardosa, T Solomon. Human Enterovirus 71
Disease in Sarawak, Malaysia: A Prospective Clinical, Virological and
Molecular Epidemiological Study. Clinical Infectious Diseases 2007; 44:646–56
� MH Ooi, SC Wong, A Mohan, Y Podin, D Perera, D Clear, S del Sel, CH Chieng,
PH Tio, MJ Cardosa and T Solomon. Identification and validation of clinical
predictors for the risk of neurological involvement in children with hand,
foot, and mouth disease in Sarawak. BMC Infectious Diseases 2009, 9:3.
� Etc….
Something simpler
in the clinic
� Between 15 April and 30 June 1997, 31 previously
healthy infants and young children in Sarawak died
after a short febrile illness against a background
of an outbreak of HFMD in the State.
� Sibu was badly affected during this outbreak as 11
of the death cases were reported from Sibu
followed by Sarikei with 7 death cases.
http://www.sarawak.health.gov.my/hfmd.htm
Clinical Research Leading to Change
http://www.sarawak.health.gov.my/hfmd.htm
Health Education Activities
� Health education pamphlets, radio talks
Enforcement of Legislation
� Delegation of authority by State Health Director to Divisional
Health Officers to close tadika/taska and kindergartens using
Section 7(2) Protection, Public Health Ordinance 1999 Sarawak.
Interagency Assistance
� Sanitary inspection, physical examination of all enrolled children at
� Recommend for immediate closure of all primary schools for 14
days, should the number of cases continue to increase in the State
Management Protocols
� Observation and isolation; and strict universal precautions
� MH Ooi, SC Wong, P Lewthwaite, MJ Cardosa, T Solomon. Clinical
Features, Diagnosis and Management of Enterovirus 71.
www.thelancet.com/neurology Vol 9 Nov 2009.
The developmental outcome of neonates
with PPHN managed with MgSO 4 –
preliminary results
� 2004-2007: 33 out of 36 survived
� 16 contactable so far (early 2011)
� 13 assessed:
� 1 has hearing impairment
� 2 has intellectual disability
� 9 showing weakness in language development despite
“normal” overall ability
� If proven: need to emphasize and advice parents re
early language development
Ref: Toh TH, Chieng CH, Wong SC; 2011

�Contributing towards
international health data
�Many examples – here is one
Toh Teck Hock, Nurhilda Abdullah, Chua Soh Yian, Muhamad
Rais Abdullah, Islia bt Nahazatul, Chieng Lee Ong. BMI, BP,
Visual Acuity and Hearing Status of Special Olympics
Athletes in Sarawak. In press.
Methodology:
Health data were collected by trained health
professionals under HAP held in conjunction with
Sarawak Special Olympics State Games between
17-18 April 2010.
N = 73 for children (less than 18 years)
BP in children

How does this project helps?
� Contribution towards international data
for people with intellectual disability
� Helps bring awareness among adult caregivers
� Primary intervention as well as secondary
/ tertiary interventional programmes
Conclusion
� Clinical Research is:
� a world-wide trend (and “flu-like”)
� about evidence-based practice
� doable at any level / setting no matter
how simple / sophisticated
� Clinical Research in children health does
improve the care clinicians provide
Many other potential topics
�Obesity and interventional studies
�Environmental effects on children
development and behaviours
�Child abuse and at risk group
�Parenting
�………
A Key Event of National Early Childhood Intervention Council