1. What is a Clinical Research?
1;Any investigation in human subjects intended to discover or verify the
clinical, pharmacological and other pharmacodynamic/kinetic;;adr;;toxicity
& efficacious effects of an investigational product(s)
Clinical research may need to conduted in certain study subjectsgroups
includes;; childern;; women;;the elders to gain drug development approch
in these groups.
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2;Clinical trials translate results of basic scientific research into better
ways to prevent, diagnose, or treat disease
The more people take part, the faster we can:
- Answer critical research questions
- Find better treatments and ways to prevent disease
3;This process of stating must consider a series of
questions.
-What data / decision is neede
-Is a specific trial required?
-Which trial design will deliver what is required?
-What use will be made of the results?
-What hypothesis is being tested or what are the precise
objectives?

2. Children are not just “little adults,” and lack of data on
important pharmacokinetic and pharmacodynamic difference
has led to several effectable situations in paediatrics .
The rate and extent of organ function development and
thedistribution, metabolism, and elimination of drugs differ not
only between pediatric versus adult patients but also among
paediatrics age groups .
The effectiveness and safety of drugs may vary among various
age groups and from one drug to another in pediatric versus adult
patients

3. PEDIATRICS AGE CLASSIFICATION ;
 Preterm newborn infants
 Term newborn infants {neonates}
(0 to 27 days)
 Infants and toddlers (28 days to
23 months)
 Children (2 to 11 years)
 Adolescents [12 to 16/18 years )
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4. PRE-TERM NEW BORN INFANTS
The study of medicinal products in pre-term
newborn infants presents special challenges
because of the unique pathophysiology
and responses to therapy in this population.
The complexity of and ethical considerations
involved in studying pre-term newborn
infants suggest the need for careful protocol
development with expert input from
neonatologists and neonatal pharmacologists.
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5. Important features that should be
considered for these patients include ;
 Gestational age at birth and age after birth (adjusted age)
 Immaturity of renal and hepatic clearance mechanisms
 Protein binding and displacement issues (particularly bilirubin)
 Penetration of medicinal products into the (CNS)
 Unique neonatal disease states (e.g., respiratory distress
syndrome of the newborn, patent ductus arteriosus, primary
pulmonary hypertension)
 Unique susceptibilities of the preterm newborn (e.g., necrotizing
enterocolitis, intra-ventricular hemorrhage, retinopathy of
prematurity)
 Rapid and variable maturation of all physiologic and
pharmacologic processes leading to different dosing regimens
with chronic exposure; and
 Transdermal absorption of medicinal products and other
chemicals.
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6. NEONATES (O TO 27 DAYS )
 Although, term newborn infants are developmentally
more mature than preterm newborn infants, many of the
physiologic and pharmacologic principles also apply to
term infants.
 Vd of medicinal products may be different from
those inolder pediatric patients because of
different body water and fat content and
high body-surface-area-to-weight ratio.
 BBB is still not fully mature and medicinal
products and endogenous substances
(e.g., bilirubin) may gain access to the CNS with
resultant toxicity.
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 Oral absorption of medicinal products may be less
predictable than in older pediatric patients.
 Hepatic and renal clearance mechanisms are
immature and rapidly changing; doses may need to
be adjusted over the first weeks of life.
 Many examples of increased susceptibility to toxic
effects of medicinal products result from limited
clearance in these patients (e.g., chloramphenicol grey
baby syndrome).
 On the other hand, term newborn infants may be less
susceptible to some types of adverse effects
(e.g.,aminoglycoside nephrotoxicity) than are patients in
older age groups.
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8. INFANTS AND TODDLERS
(28DAYS TO 23MONTHS) ;
 Oral absorption becomes more reliable.
 This is a period of rapid CNS maturation, immune
system development and total body growth.
 Hepatic and renal clearance pathways continue to
mature rapidly.
 By 1 to 2 years of age, clearance of many drugs on
a mg/kg basis may exceed adult values.
 The developmental pattern of maturation is
dependent on specific pathways of clearance.
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9. CHILDREN (2 TO 11 yrs):
 Most pathways of drug clearance (hepatic and renal)
are mature, with clearance often exceeding adult
values. Changes in clearance of a drug may be
dependent on maturation of specific metabolic
pathways.
 The onset of puberty is highly variable and occurs
earlier in girls, i.e. as early as 9 years of age.
 Puberty can affect the apparent activity of enzymes
that metabolize drugs, and dose requirements for
some medicinal products on a mg/kg basis may
decrease dramatically (e.g., theophylline).
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10. ADOLESCENTS:12 TO 16-18yr ;
 This is a period of sexual maturation; medicinal products may
interfere with the actions of sex hormones and impede
development. In certain studies, pregnancy testing and review
of sexual activity and contraceptive use may be appropriate.
 This is also a period of rapid growth and continued
neurocognitive development.
 Many diseases are also influenced by the hormonal changes
around puberty (e.g., increases in insulin resistance in
diabetes mellitus, recurrence of seizures around menarche,
changes in the frequency and severity of migraine attacks and
asthma exacerbations). Hormonal changes may thus
influence the results of clinical studies.
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11. Major Physiologic Variations In
Pediatrics
 Generally, in children and elderly people, drugs and biological
products behave similarly than in 18-65 year-old population.
The important pharmacokinetic variables such as immature or
aging enzyme metabolism systems as well as elimination rates
affected by immature or aging organs of excretion must be
properly adjusted.
 In neonates, the gastric pH is biphasic- High in first few days
of birth and decreases by 30th day, but takes 5-12 years for
the adult pattern and a constant value to emerge.
 On the other hand, methylation pathway, which is not
important in adults, is well developed in children.
 Furthermore, Acetaminophen is less toxic to children than
adults, because it utilizes sulphate metabolic pathway.
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12.  The informed consent process is the foundation ofany ethical
research.Researchers should have a clear understanding of the
process on a theoretical and practical level to conduct ethics
studies, to improve parents’/patients’ understanding and
expectation, and to improverecruitment rates.
 in accordance with the Declaration of Helsinki on ethical principles
In any research on human beings, each potential subject must be
adequately informed of the aims, methods, anticipated benefits
and potential hazards of the study and the discomfort it may
entail. He or she should be informed that he or she is at liberty to
abstain from participation in the study and that he or she is free
to withdraw his or her consent to participation at any time.
 As a rule, a pediatric subject is legally unable to provide informed consent.
 Therefore, pediatric study participants are dependent on their
parent(s)/legal guardian to assume responsibility for their participation in
clinical studies.
 Fully informed consent should be obtained from the legal guardian in
accordance with regional laws or regulations. All participants should be
informed to the fullest extent possible about the study in language and
terms they are able to understand.
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Informed consent

13.  Phase I studies are usually avoided in paediatrics because the risk to a
child is more than minimal. The chance of having a significant clinical is minimal.
Institutional Review Board/Independent Ethics Committee
(IRB/IEC):
The roles and responsibilities of IRB’s/IEC’s as detailed in ICH E6 are critical to
the protection of study participants. When protocols involving the pediatric
population are reviewed, there should be IRB/IEC members or experts consulted
by the IRB/IEC who are knowledgeable in pediatric ethical, clinical, and
psychosocial issues
When studies are conducted in the pediatric population, an attempt should be
made to include individuals representing the demographics of the region and the
disease being studied, unless there is a valid reason for restricting enrollment.
Investigators should be fully aware before the start of a clinical study of all
relevant preclinical and clinical toxicity of the medicinal product.
To minimize risk in pediatric clinical studies, those conducting the study should
be properly trained and experienced in studying the pediatric population,
including the evaluation and management of potential pediatric adverse events.

14. Types of paediatric clinical trials
•Paediatric formulation studies.
•Pharmacokinetic studies
•Pharmacodynamics studies
•Efficacy & safety study
•Cohort study
•Case control study
•Trail design for rare diseases;;{ involves open
protocol design;;Cross over design;;suurogate end
point study;;meta analysis }