Prof' Dr' Niranjan Mohanty

1
Basic Research Methods
BY Prof. (Dr.) Niranjan Mohanty
2
The methodology for research and evaluation of
homoeopathic medicine should be based on basic
principles and the methodology should guarantee
the safety and efficacy of homoeopathic
therapies.
3
RESEARCH
Research is a quest for knowledge through
diligent search or investigation or experiment
aimed at the discovering and interpretation of
new knowledge. (WHO)
DEFINITION
Research is an art of scientific investigation.
4
RESEARCH
A systematized effort to gain new knowledge
(Redman)
DEFINITION
A careful investigation or inquiry specially
through search for new facts in any branch of
knowledge (Advanced learners Dictionary)
5
RESEARCH METHODS / SCIENTIFIC METHODS
Definition
Scientific method is a systematic body of
procedures and technique applied in carrying out
our investigation or experimentation targeted at
obtaining new knowledge (WHO).
6
RESEARCH TECHNIQUE

• Library Research
• Field Research
• Laboratory Research

7
It is a way to systematically solve the research
problems.
RESEARCH METHODOLOGY
Science of studying how research is done.
8
Qualitative
RESEARCH APPROACHES
Quantitative
Simulation
Experimental
Inferential
9
Theoretical / Conceptual
Empirical
Philosophical
Basic and applied
Other categories
10
EMPIRICAL RESEARCH

• Health research mainly follows the empirical
  approach.
• It is based on observation and experience more
  than upon theory and abstraction.
• e.g. Epidemiological Research depends upon
  systemic collection of observations.
• It can be qualitative quantitative.
• Health Science Research deals with information
  of a quantitative nature.

11
Empirical Research involves

• The identification of the population of
  interest.
• ? The characteristics (variables) of the
  individuals (units) in the population.
• ? The study of variability of these
  characteristics among the individuals in the
  population.

12
Quantification in Empirical Research

• Measurement of variables.
• ? Estimation of population parameters.
• ? Statistical testing of hypothesis.

? Empirical research relies on experience or
observation without due regard to system or
theory. ? We can call it experimental type of
research.
13
THEORETICAL / CONCEPTUAL RESEARCH
? It is related to some abstract idea(s),
theory. E.g.   In abstraction with mathematical
models.    Advances in understanding of
disease occurrence and causation cannot be
made without a comparison of the theoretical
constructs with that which we actually
observe in populations. ? Empirical
theoretical research complements each other in
developing an understanding of the phenomena, in
predicting future events.
14
Basic / fundamental / pure
Basic and applied
Applied / Action
15
BASIC / FUNDAMENTAL / PURE

• It means formation of theory or generalization.
  
• Basic research is usually considered to
  involve a research for knowledge without a
  defined goal of utility or specific purpose.

16
APPLIED / ACTION
? Solution for immediate problems. ? Applied
research is problem oriented.
OTHER CATEGORIES OF RESEARCH

• ? Longitudinal / one time.
• Field setting / laboratory / simulation.
• ? Clinical / diagnostic.
• Historical.
• ? Conclusion oriented / decision oriented.

17
Bio-medical (Cellular Research)
Health Research Triangle
Behavioral (Beliefs / attitudes / practices in
the society by man)
Health Research (Environmental)
18
SCIENTIFIC FOUNDATIONS OF RESEARCH ORDER
?  Scientific method is not common sense. ? In
arriving at conclusion common sense cant be
employed e.g. Draft of air causes Allergic
Rhinitis. ? To arrive at conclusion an
organized observation of entities or events
which are classified or ordered on the basis of
common properties and behaviors are required.
19
? It is this commonality of properties and
behaviors that allows predictions which
carried to the ultimate, become laws e.g. A
number of Allergic Rhinitis cases are studied
and it is found a number cases are having a
group of common causes from which prediction is
made and there after etiology become conclusive
as from Allergens.
20
SCIENTIFIC FOUNDATIONS OF RESEARCH INFERENCE AND
CHANCE
? Reasoning or inference is the force of
advances in research. ? In terms of logic, It
means that a statement / or a conclusion ought
to be accepted because one or more other
statements / premises (evidence) are true. ?
Inferential suppositions, presumptions or
theories may be so developed, through careful
constructions, as to pose testable hypothesis.
21
SCIENTIFIC FOUNDATIONS OF RESEARCH INFERENCE AND
CHANCE

• The testing of hypothesis is the basic method
  of advancing knowledge in science.
• ? Two distinct approaches or arguments have
  evolved in the development of inferences. They
  are such as deductive and inductive.

22
SCIENTIFIC FOUNDATIONS OF RESEARCH INFERENCE AND
CHANCE
?   In deduction, the conclusion necessarily
follows from premises (evidence) / statements,
as in syllogism e.g. All A is B, all B is
C therefore all A is C or in algebraic
equations. ? Deduction can be distinguished by
the fact that it moves from the general to the
specific.
23

• It dose not allow for the elements of chance
  or uncertainty.
• ? Deductive inference, therefore are suitable
  to theoretical research.

24
INDUCTION
Inductive reasoning is distinguished by the fact
that it moves from the specific to the general
(from sample to population). It builds-
? Health research being primarily empirical
depends entirely upon inductive reasoning. ? The
conclusion dose not necessarily follows from the
premises or evidence (facts). We can say only
that the conclusion is more likely to be valid it
the premises are true, i.e. there is a
possibility that the premises may be true but the
conclusion is false.
25
Method of difference
Frequency of disease is markedly dissimilar under
two circumstances. Ex. Lung cancer (Smoker /
Non-smoker)
MILLS CANONS OF INDUCTIVE REASONING
Method of concomitant variation
Method of Analogy
Method of agreement
Different factors that are found to be associated
with the presence of disease. Ex.- Hepatitis A
with patient contact, overcrowding poor hygiene.
If the distribution / frequency effect are common
then to suggest commonality in cause. Ex.
Hepatitis B / Cancer Liver.
It is the dose response effect. Ex.- Leukaemia
with increased radiation. Increased goiter with
decreased iodine level.
26
EVALUATION OF PROBABILITY
?  It is a critical requirement in research
design. ?   Evaluation of probability ensures
validity. ?   The most salient elements of
design, which are meant to ensure the integrity
of probability and prevention of bias,
are a)  Representative sampling. b) 
Randomization in the selection of study
group. c)  Control group for comparison. d)   
Blinding of experiment. e)   Use of probability
(statistical) method in analysis
interpretation. Probability is a measure of
uncertainty or variability of the characteristic
among individuals in the population.
27
HYPOTHESIS (A guess or imaginary idea)
? Hypothesis are carefully constructed statements
about a phenomenon in the population. ? It may be
generated by deductive or inductive reasoning
from prior observations.
SOURCE OF HYPOTHESIS
a)       General culture b)       Scientific
theory c)       Analogies d)       Personal
experience
28
QUALITIES OF WORKABLE HYPOTHESIS
a)       Specific b)       Conceptually
clear c)       Related to available
technique d)       Capable of empirical
test e)       Simple
29
UTILITY IN RESEARCH
a)       Hypothesis gives point to
inquiry. b)       Hypothesis helps in deciding
in which to proceed. c)       Hypothesis helps
in selecting pertinent facts. d)      
Hypothesis helps in drawing specific conclusion.
30
SELECTION OF STUDY DESIGN
Clinical research aimed at evaluating
homoeopathic medicine should incorporate the
conventional concepts of research design, such as
randomized controlled trials or other types of
clinical studies, such as observational studies.
31
Objectives specific to the assessment of
homoeopathic medicine through clinical research
are to

• Evaluate homoeopathic medicine in the own
  theoretical framework (e.g. mechanistic
  studies).
• Evaluate homoeopathic medicine in the
  theoretical framework of conventional medicine
  (e.g. mechanistic studies).

32

• Compare the efficacy of different systems of
  homoeopathic medicine and / or conventional
  medicine.
• ? Compare the efficacy of different
  homoeopathic practices within a system of
  traditional medicine.

33
Research synthesis studies
Research synthesis studies including
meta-analyses, may be useful as supporting
evidence for a health claim.
34
Single-case design
It has the advantage of being adaptable to the
clinical needs of the patient and the therapeutic
approach of the practitioner. Such designs are
appropriate for the development of research
hypotheses, testing those hypotheses in daily
clinical practice and refining clinical
techniques.
35
Black-box design
? The treatment and all of its components are
delivered as they would be in the usual clinical
situation. ? No component of the treatment
package is isolated and studies
independently. ? Study of homoeopathic medicine
can be also be undertaken in a black-box
manner.
36
Ethnographic design
Document the social and cultural context in which
a traditional practice emanates may be
appropriate in situations where there is no
specific literature or other documentation.
37
Observational design
They seek, as far as possible, not to influence
the individual doctor-patient relationship with
respect to indications, and the selection of and
carrying out the treatment.
38
Study of outcome measure
Appropriate outcomes may include quantitative and
qualitative outcomes primary and secondary
outcomes and generic and/or highly specific
outcomes.
39
Selection of patients
Publication of the study requires a clear
description of the patients using both
traditional conventional terms The source of
patient under the study should be
comprehensively described along with detail of
the recruitment process. The inclusion
exclusion criteria should be completely
described rationalized.
?
?
?
40
?
Any potential bias in patient selection,
recruitment and enrolment should be excluded.
Investigators should be aware any potential
errors that may occur when studying homoeopathic
medicine out of context and without reference to
homoeopathic theories concepts.
?
41
Sample size
The number of patients in study needs to be
adequate, in order to be able to determine any
clinically important differences between the
study groups.
42
The control group
May involve

• Well established treatment
• Non-treatment
• Different doses of the same treatment
• Sham or placebo treatment
• Full-scale treatment
• Minimal treatment
• Alternative treatment

43
Randomization
Tremendous advance in developing comparable
groups to assess therapeutic interventions.
44
Blind assessment
A critical component of conventional evaluation
of therapeutic interventions.
It is essential that this be noted in the
evaluation of a validity of a study and that the
judgment on its validity is applied consistently
across all systems of conventional homoeopathic
medicine.
45
Evaluation of Quality of Life
The WHO QOL user manual, developed by the WHO
programme on mental health, can be used to help
evaluate the results of clinical research.
46
Other issues related to therapeutic interventions
1. Description of the therapeutic
intervention. 2. Description of the reasons for
the selection of the therapeutic
intervention. 3. Description of the rationale
for the choice of the study outcomes.
47
Other issues related to therapeutic interventions
4. Description of the outcome measurements,
including a review of the validity and
reliability of the measurements. 5. A
comprehensive protocol for taking the
measurements (including how and when the
measurements were taken). 6. A clear statement
of which expected outcomes the statistical method
was based on.
48
Issues should be considered
The type of intervention must be clearly defined.
The training skills and experience of the
homoeopathic medical practitioner should be taken
into account.
49
If the setting as an important component of a
treatment, its essential features must be
described.
The dose, frequency and duration of a treatment
must be described completely.
50
The duration of follow- up should be clearly
stated.
Temporal considerations need to be assessed and
noted.
51
Steps of research designing
Selection of the sample ?      It should be
unbiased ?      Sufficiently large in size to
represent population under study.
52
a) Sample size
Calculating the size of the sample computer
programs are available e.g. EPIINFO.

• For descriptive study
• The calculation of sample size depends on two
  parameters
•   Width of confidence interval (?)
• Confidence of co-efficient (1-?)

53

• Estimating a population proportion (P)
• Suppose we want to conduct a survey to determine
  the prevalence (?) of a relatively common disease
  in the community.
• Confidence co-efficient (1-?) 95
• Width of this interval (?) 10
• Make a guess as to the value of ? 30
• Formula n (Z 1-? /?) 2 P (1-P)
• n (1.96 / 5)2 (30 x 70) 323

54
ii) Suppose we want to estimate the average
daily caloric intake of people in a
community. Confidential co-efficient (1-?)
95 Width of interval (?) 50 cal. Obtain the
standard deviation (?) 150 cal. X ? Z (1-?) ? /
? n Sample size n (1.96 150 / 50) 2
35  iii) Estimating relative risks or odd ratios
consult various computer programs.
55

• For analytical study
• The sample size 
• i) Testing equality of two proportions 
• n Z1-?? 2?-(1-?-) - Zp ? ?1(1-?1)
  ?2 ( 1- ?2) / ?2
•   n 640
• ii) Sample size for a case control study
• Comparison of two population means
• n (Z 1-? - Z?) 6 / ? 2
• iv) Comparison of more than two groups and
  multivariate methods.

56
For Qualitative Data
N 4pq/L2 Where p is the positive character,
q 1-p L allowable error, 10 or 20 of p
For Quantitative Data
L2?/?n or ?n2?/L or n 4?2/L2
57
b) Sampling methods
i) Simple random sampling - Choose random
number from the table. ii) Stratified
sampling - (Selecting 50 male 50
female) iii) Systemic sampling - Systematically
it is chosen.
58
iv) Cluster sampling - Cluster may be identified
(households) and random samples of cluster.
v) Multistage sampling - In several stages.
59
Specify the nature of study

• Human studies
• Interventional studies
• Observational studies
• Pre-clinical evidence
• In vitro laboratory investigations
• Other mechanistic studies

60
Observational study
Investigator does not have control over the
exposure or the intervention.
61
Observational study
Cohort studies
Case controlled studies Cross
sectional studies Uncontrolled case series or
cohort studies
62
Observational study
Time series studies
Ecological or cross
population studies Descriptive
epidemiology Case reports.
63
Cohort studies
? Cohort studies compare the outcome of
subjects who have received a specific exposure
with the outcome of subjects who have not
received that exposure.
? A group of persons exposed to same sort of
environment e.g. new born mother exposed to
radiation.
64
- Prospective Follow-up of morbidity and
mortality in infants from birth to one year of
age. - Retrospective Number of persons in
the same population who suffered from typhoid in
last 5 years.
65
Case control studies Most of the experimental
studies need a control as a yard stick of
evidence Example - Growth of child with
constitutional medicine control group with no
medicine. Control group must be identical. To
rule out subjective bias in subjects under study
single or double blind trial should be made.
66
Cross sectional studies (Non experimental) Such
studies are one time or at a point of time study
of all persons in a representative sample. It is
conducted in field and not in laboratories. Exampl
e - Examination of children 2- 12 yrs and
classify their nutritional grade.
- Prevalence of pregnancy in age group
of 20-25 yrs.
67

• Uncontrolled studies
• Uncontrolled case series studies depict outcome
  in a group without comparing to a control group.

68
? Time series studies compare outcomes during
different time periods. E.g. whether the rate of
occurrence of a particular outcome during one
five-year period changed during a subsequent
five- year period. ? In ecological studies the
rate of a disease is compared across different
population. Investigators seek to identify
population traits that may cause the disease.
69
? Case reports describe observations of single
subjects or a small number of subjects. ?
Descriptive epidemiology refers to study
designs that assess parameters related to the
frequency and distribution of disease in a
population, such as the leading cause of death.
70
Descriptive studies
? Belongs to observational categories of
studies. ? Not aimed specifically to test a
hypothesis. ? Allows to generate hypothesis. ?
Prevalence survey is an example of such study.
71
HOW TO CONDUCT DESCRIPTIVE STUDIES
Descriptive studies entail the collection,
analysis and interpretation of data. - Both
qualitative and quantitative techniques may be
used including. -   Questionnaires -  
Interviews -   Observation of participants -  
Service statistics -   Documents, describing,
communities, groups , situations, programmes,
and other individual or ecological units.
72
KINDS OF DESCRIPTIVE STUDIES

• Case series - A series of created cases
  with out group.
• - It is to calculate proportional distribution
  which consist simply of total number of cases
  belong to specific category of age, sex or other
  characteristics.
• -  It is needed to provide baseline data for
  the design of further studies or action.
• -   Occurrence and distribution of disease in
  population is studied according to specific
  characteristics.

73
KINDS OF DESCRIPTIVE STUDIES

• Community diagnosis or needs assessment.
• Epidemiological description of disease
  occurrence.
• Descriptive Cross sectional studies or
  Community survey.
• Ecological descriptive studies.

74
ANALYTICAL STUDIES
?   Observational studies are termed analytical,
where establishing a relationship (association)
between risk factor (etiological agent) and an
out come (disease) is the primary goal. ?   In
this type of study, hypothesis testing in the
primary tool of inference. ?    The basic
approach in analytical studies is to develop a
specific, testable hypothesis and to design the
study to control any extraneous variables. ?  
The approach varies according to the specific
strategy used.
75
1) Case control studies It is designed primarily
to establish the cause of the disease by
investigating association between exposure to a
risk factor and the occurrence of the disease.
76
Exposure (With characteristic or risk factor)
Cases (Those with conditions)
Unexpected (Without characteristic or risk factor)
Expose (With characteristic or risk factor)
Control (Those without condition)
Unexpected (Without characteristic or risk
factors)
77
Example
Chewers of tobacco
Case of Oral cancer
Non chewers of tobacco
Chewers of tobacco
Those free of oral cancer
Non chewers of tobacco
78
2) Prospective cohort studies  The common
strategy of cohort studies is to start with
reference population (or a representative sample
there of) some of whom have certain
characteristics or attributes relevant to the
study (exposed group) with others who do not have
those characteristics (unexposed group). Both
group should be, at the out set of the study, be
free from the condition(s) under consideration.
Both groups are then observed over a specified
period to find out the risk each group has of
developing the condition(s) of interest.
79
(No Transcript)
80
(No Transcript)
81
3) Historical (Retrospective) cohort
studies   ? This can be carried out without the
continuous presence of investigators. ?
It depends upon the availability of data or
records and allows reconstruction of the
exposure cohort to a suggested risk factor
and follow up of their mortality
morbidity over time.
82
(No Transcript)
83

• Prognostic cohort studies 
• These are a special type of cohort study used to
  identify factors that might influence the
  prognosis after a diagnosis or treatment. 

84

• Analytical cross sectional studies 
• In this study, the investigator measures
  exposure and disease simultaneously in a
  representative sample of the population. It
  measures the association between the exposure
  variables and existing disease (Prevalence)
  unlike cohort studies, which measures the rate of
  developing disease (Incidence).

85
DESIGN
Reference population
Sample
No characteristic (No exposure) and no disease
Characteristic (Exposure) and disease
No characteristic (No exposure) and disease
Characteristic (Exposure) and no disease
86
Interventional study

• Investigator controls whether the subjects
  receive an exposure or an intervention.
• Interventional studies provide the strongest
  evidence for an effect.

87
Interventional studies In these there are three
phases.  - Diagnostic / Identification. -
Intervention by treatment. - Assessment phase
for result.
88
Experimental studies-  - Experimental or
trial are made. - A drug is given and
results are wanted.
89
Advantages of Experimental Approach
1) The ability to manipulate or assign
independent variables   Example In an
evaluation of the efficacy of a therapy, children
of a certain age and with certain other
characteristics may be assigned at random or in
method pairs to Physicians and nurses. In two
groups (Control / test). It may be possible to
manipulate the dose, frequency of repetition.
90
Advantages of Experimental Approach
2) The ability to randomize subjects to
experimental and control groups   ?  By
randomization the distribution of some
extraneous variables will be equalized
between the two groups.  ?   In addition,
randomization provides a basis for the
calculation of appropriate probabilities of
error in the inference. 3) The ability to control
confounding and eliminate sources of spurious
association  It is possible especially in
animal experiment than in observational studies.
91
Advantages of Experimental Approach
4) The ability to ensure temporality    In
experimental study, it is feasible to determine
the preceding or succeeding consequences of
the intervention, particularly these of the
case control and cohort design. 5) The ability
to replicate findings   In experimental studies
it is replicated than observational
studies. Replication satisfies the consisting
requirement in causation.
92
Disadvantages of Experimental Approach

• Lack of reality
• Observational methods deal with more realistic
  situations
• 2. Difficulties in extrapolation
• Results in animal models cannot readily be
  extrapolated in human population
• 3. Ethical problems
• It is unethical to test the efficacy or side
  effect of a drug with out critical evaluation in
  small groups.

93
Disadvantages of Experimental Approach
4. Difficulties in manipulating the independent
variable It is virtually impossible, for
instance, to assign smoking habit at random to
the experimental or control groups. 5. Non
representative of samples Many experiments are
carried out on captive population or volunteers,
who are not representative of population.
94

• Experimental and Quasi experimental studies 
• An experiment is the best epidemiological study
  design to prove causation. It can be viewed as
  the final or definitive step in research process,
  a mechanism for confirming or rejecting the
  validity of ideas, assumptions postulates and
  hypothesis. The experimenter (Investigator) has
• control of the subjects
• (b) the intervention out come measurements. 

95
Purpose of experiment  The design of experiment
serves the purpose of ensuring valid data
relevant to the hypothesis as economically
(maximum statistical power with minimum cost and
convenience) as possible.  Although an
experiment is an important step in establishing
causality, it must be remembered that it is often
neither feasible nor ethical to subject human
beings to risk factors in etiological studies,
experiment therefore after confirm to the
clinical trial of real drugs or therapies which
would be potentially more beneficial and
ethically justifiable.
96
THE EXPERIMENTAL DESIGN 
Reference (target) population
Experimental (study) population
Non-participant
Participant population
Intervention group
Control group
Compare
Out come
Out come
97

• There are two types -
• R.C.T (Randomized Clinical Trial)
• C.I.T (Community Intervention Trial)

98
The randomized clinical trial (R.C.T) The most
commonly encountered experiment in health science
research and research strategy, by which evidence
of effectiveness is measured, is the randomized,
controlled, double blind clinical trail, commonly
known as R.C.T.
Experimental group
Exposure
Pre-testing Baseline
Initial status
Identity target population to whom intervention
may apply
Select a probability sample
Assign at random
99
VARIOUS PURPOSES FOR WHICH CLINICAL TRIALS ARE
UNDERTAKEN
a. Properly trials. b. Therapeutic trials
palliative curative. c.  Study of side effects
of drugs. d.  Risk factor trials (proving
etiology of disease in animal model) e. Medical
counseling. f.  Diet, exercise change of life
style habits. g. Health care services /
personnel. h. Treatment regimens.
100
Traditionally clinical trial of new therapies or
devices pass through four phases-
a.  Phase I clinical trial  ? Study of
pharmacological and toxicological effects on
animal model preceded by human experiment. ?
It includes studies of volunteers to observe
changes in various systems ? Requires to carry
in research beds in any institution. ?
 Requires close supervision ? This phase is of
short duration ( Usually one to two months) ?
Requires experts / highly developed laboratory
facilities.
101
Traditionally clinical trial of new therapies or
devices pass through four phases-
b.  Phase II Clinical trails ? It is to carry
out on volunteers selected to strict
criteria. ?  To assess effectiveness of drug,
dose. ?   To investigate its safety. ?
 Relationship of drug.
102
Traditionally clinical trial of new therapies or
devices pass through four phases-
c. Phase III Clinical trial ?  Drug is tested on
patient ?  Strict criteria for inclusion
exclusion are observed. ?  It is conducted in
O.P.D / I.P.D ?  In this phase usually reported
to research journals results are used by
regulatory agencies. ? To provide licensed
for general public use.
103
Factors influences the design and analysis of
clinical trials (Phase III)
-       Agent / treatment / Experimental
factors. -                     Conditions to be
treated. -                     The target
population. -                     Ethical
issues. -                    Outcome to be
measured. -                     Side
effects. -                     Study
instruments.
104
-          Blinding -          Stopping
rule -          Plan for analysis. -         
Selective attrition -          Method for
ensuring integrity of the data. -         
Choice of design. -          Time required.
105
Traditionally clinical trial of new therapies or
devices pass through four phases-
d.   Phase IV clinical trial ? Purpose is to
re-assess the effectiveness. ? Safety. ?
Acceptability. ? Effect of continuous use.
106
COMMUNITY INTERVENTION TRIALS (C.I.T)
? It is usually directed at a patient group with
specific health conditions ? Randomization is
done in communities rather than individuals ?
Example Rhus tox. 1M as prophylaxis against
Chicken pox. ? A group (Unit) is taken as test
group where another group (Unit) is taken as
control group.
107
Accuracy of the inference depends on a) On the
accuracy of the information collected.
b)  On the representative ness of the subjects
observed to the larger group of subject in
the population. c)  On the accuracy of
the statistical method used to draw the
inference.
108
Errors in the inference
Two common sources of errors that needs to be
controlled result from problem with reliability
and validity.
109
RELIABILITY
If the observations are repeated under similar
conditions the inference should to be
similar.  ? Reliability of the sample is
achieved by selecting a large sample. ?
Reliability is measured by using random
error
110
VALIDITY
?  The inference should be reflection of the
true nature of the relationship. ? Validity is
achieved by insuring the sample selection is
unbiased. ?  Validity is measured by using bias.
111

Statistical Tools or Tests of Significance Z
test Z X - ? / SE (X) (between sample
means) Where X Sample mean ?
Population mean SE Standard error Z
Observed difference between two sample means /
Standard error of difference between two sample
means (between two sample means)
112

• Requirements to Apply Z Test
• The sample or samples must be randomly selected.
• 2. The data must be quantitative.
• 3. The variable is assumed to follow normal
  distribution in the population.
• 4. The sample size must be larger than 30.

113
t test Requirements to Apply t Test 1. The
sample or samples must be randomly selected. 2.
The data must be quantitative. 3. The variable is
assumed to follow normal distribution in the
population. 4. The sample size must be less than
30. t X - ? / SE (X) Where X
Sample mean ? Population mean SE Standard
error
114

• Chi square Test (?2 test)
• It has got the following three very important
  applications in medical statistics as tests of
• Proportion To find significance in same type of
  data.
• Association between two events.
• Goodness of fit To test fitness of an observed
  frequency distribution of qualitative data to a
  theoretical distribution.

115

• To apply ?2 test
• Three Essential Requirements
• A random sample
• Qualitative data
• Lowest expected frequency (value) not less than 5

?2 ? (O E)2 E Where O
Observed value E Expected value
116
Variance Ratio Test (F test) This means
comparison of sample variance. It is applied to
test the homogeneity of variances. F S12 /
S22 S12 Variance of first
sample S22 Variance of second sample
(S12 gt S22)
117
ANOVA Test (Analysis of Variance Test) This
test is not confined to comparing two sample
means but more than two samples drawn from
corresponding normal population.
118
Model case
119

• Introduction
• Definition of the problem - Define the
  problem you intend to study such as Smoking and
  Lung Cancer, Cholesterol C.A.D etc.
• Relevance of the problem with fields of
  application of proposed research result.
• Rationale of the study - What necessitate to
  carry out the study.

120

• Example Psoriasis
• Introduction
• Defining the problem
• World wide distribution.
• Affects 1-3 of population.
• Common in tropics. More common in winter than
  summer.

121
Relevance

• The course tends to be chronic and unpredictable
  and the disease may be refractory to treatment.
• It is difficult to treat with tropical agents.
  (Current Medical Diagnosis and Treatment by
  Tierney, Mcphee, Papadakis)
• The goal of therapy in counter system is to
  decrease epidermal proliferation and underlying
  inflammation. There is no curative agent for
  psoriasis, and the treatment only suppress the
  condition as long as administered. (Cecils Text
  Book of Medicine by Goldman and Bennett)

122
Rationale

• Isolated case studying different Journals speaks
  of cases cured with Homoeopathy.
• Individual experiences confirms it.
• Citadel Homoeopathy is flooded with information
  to comb acts the disease psoriasis.
• But lack of statistical data hence it is
  required to continue the scientific world

123

• 2 .Review of literature
• Critically review the literature on the problem
  under study
• Any such work done by others in the past
• Clarify
• Want to confirm the findings
• Challenge the conclusion
• Extend the work further
• Bridge some gaps in the existing knowledge

124
Example Psoriasis
2 . Review of literature
? It is a heredo- familial disease brought on by
stress, anxiety, mental trauma, fever, physical
injury, digestive upsets, etc. on a genetic
constitution.
125
Immunopathological
Etiology
Genetic
Dermal
Biochemical
126
Genetic

• Susceptible gene at the distal end of
• chromosome 17q.
• Marker appear to be independent of
• HLA CW 6.
• Those antigen are linked with CW6 with which
  psoriasis is strongly associated.

127
One parent psoriatic
15 chances
128
Both parent psoriatic
50 chances
129
Non psoriatic parents
10 chances
130
Biochemical

• Increased levels of prostaglandins. Leukotrines
  and hydroxyeicosatetraenoic acids in the
  epidermis.
• Decreased cAMP and increased cGMP are found in
  lesions and beta-adrenoceptor antagonistic drugs
  may exacerbate psoriasis by inhibiting cAMP
  formation.
• Polyamines are elevated in lesional skin, due to
  increased activity of ornithine decarboxylase
  and may be intimately associated with cellular
  proliferation
• The calcium-calmodulin complex may regulate
  epidermal cell-proliferation by influencing
  phospholipase A2 and cAMP phosphodiesterase
  activity.

131
Immunopathological

• Activation complement system
• Attraction of neutrophils to the area.
• Elevation of certain interleukins (IL-1, IL-2,
  IL-6 and IL-8) and growth factors (TNF ?, TGF ?)
• Adhesion molecules are expressed or up regulated
  in lesions of psoriasis.
• The dermal mononuclear infiltrate is mainly of T
  - lymphocytes, most of which are helper type.

132
Dermal
The increased epidermal cell proliferation of
psoriasis is related to the increased replication
and metabolism of dermal fibroblasts.
133
Trauma
Sunlight
Purine in diets
Precipitating factors
Infection
Drugs
Emotions
Presence of diabetes
134
PATHOGENESIS
Result from a complement mediated reaction
localized to the stratum corneum. Exogenous or
endogenous damage to the stratum corneum antigens
Formation of specific auto antibodies
Antibodies bind to the stratum corneum
135
PATHOGENESIS
Fix complement system and activate the complement
cascade. Neutrophil recruitment and
activation Release proliferation factors for
the underlying keratinocytes, resulting in
increased epidermal turnover.
136
Clinical features

• The typical distribution is extensor.
• Psoriasis exhibits itself as dry, well defined
  macules, papules and plaques of erythema with
  layer-upon-layer of silvery scales.
• The typical lesions are coin shaped, by
  confluence, big plaques of the size of the palm
  of a hand
• Slightly raised above the surface of the skin
• Koebners phenomenon
• Annular Psoriasis.

137

• The scalp is involved in almost all cases .
• Nails show three types of lesions
• Pitting.
• Separation of the distal portion of the nail
  form the nail bed and walls.
• Thickening of the nail, accompanied by the
  collection of hyperkeratotic debris under the
  nail.
• Corona Psoriatica
• The palms of the hands are involved more
  commonly .
• Lesions consist of well defined patches of
  hyperkeratosis and fissures, on eythematous
  bases
• Lesions are bilaterally symmetrical.
• Psoriasis Inversus

138
Auspitz sign
SIGNS
Candle-Grease sign (Tache de bouge).
139
Guttate psoriasis (Plaque Psoriasis, Psoriasis
Vulgaris)
Psoriasis arthropathica
Flexural psoriasis
Types
Erythrodermic psoriasis
Inverse psoriasis
Erythrodermic psoriasis
Pustular Psoriasis
140

• Diagnosis
• The family history of psoriasis.
• The typical distribution of the lesions on the
  scalp, elbows, knees, the front of the legs,
  back and nails.
• Well-defined, non-indurated, dry, erythematous
  areas with silvery layer-upon-layer scaling.

141
Diagnosis

• The candle-grease sign, Koebners phenomenon
  and pin-point bleeding upon removal of the
  scale.
• Little or no itching.
• History of previous attacks and seasonal
  variations of disease.
• Typical histopathology.

142

• Laboratory findings
• The erythrocyte sedimentation rate is usually
  increased in erythrodermic and generalized
  pustular psoriasis and there is leucocytosis in
  the latter.
• In the erythrodermic psoriasis there is loss of
  protein and iron resulting hypoproteinaemia and
  mild anemia.
• Serum and red cell folate and serum B12 tend to
  be low.
• Blood hydroxyproline is sometimes raised and
  also there is negative nitrogen balance.

143
Laboratory findings

• Uric acid level may be elevated in psoriasis,
  causing confusion with gout in psoriatic
  arthritis.
• Radiographs of affected joints can be helpful in
  differentiating types of arthritis.
• Immunoglobulin is generally normal but
  selective IgA deficiency and monoclonal IgG
  gammaglobinopathy are documented in association
  with psoriasis.

144
Syphilitic psoriasis
Differential diagnosis
Seborrhoeic Dermatitis
Pityriasis rosea
145
Prognosis
Disease is non-infectious.
General health and longevity are unaffected
though the majority of patients suffer from the
disease on and off throughout their lives.
The course is chronic with varying periods of
intermission.
Flexural, erythrodermic and pustular psoriasis
take longer to heal than the typical variety.

The palmar and nail lesions are rather resistant
to treatment
146
Use moisturizer.
Maintain a healthy weight.
Follow a nutritious diet.
Self care
Avoid sun exposure.
Take daily baths.
147
Physical General R.H.C- Chilly patient Desires
milk Aversion - sweets Thirst Great thirst,
drinks much but little at a time.
Mental General Great anguish Restlessness Fastidi
ousness
Ars. alb.
Psoriasis Free desquamation Milliary
eruption Itching, burning gt by external heat
application Dry scaly, rough skin lt cold
scratching gt external heat heat
application
148
Physical General R.H.C Hot patient Desires open
air But not too cold. lt Cold , cold
weather. Aversion - sweets
Mental General Hurried
Ars. iod.
Dry, scaly, itching Marked exfoliation of skin
in large scales, leaves a raw exuding surface
beneath. Emaciation with psoriasis. Itching lt
washing Dry, harse, dusky skin lt dry weather,
cold weather. gt open air
149
Mental General Apprhensive Indecisive Despondency
Music makes her weep.
Physical General R.H.C Chilly patient Desire-
Milk Aversion Meat, sweet, fish,
salt. Constipated Obese
Graphites
Rough, hard, persistent dry unhealthy
skin. Every little injury suppurates. Eruptions
oozing out a sticky exudation. Obstinate dryness
of skin, absence of perspiration. Itching of skin
until it is raw lt evening and night.
150
Mental General Nervous Hurried Impulse to do
violence , to do murder.
Physical General Desires- Sweet, sour, warm
drinks Aversion- Meat. R.H.C- Chilly patient.
Kali ars.
Psoriasis in numerous patches, with great
itching, causing him to sratch, till an ichorous
fluid discharges, forming a hard cake. Psoriasis
patches scale off and are replaced by smaller
ones and leave behind them a red skin. lt change
of weather.
151
Repertorial review From Synthesis
Repertory HEAD, Eruption, crushed, scars HEAD,
Eruption, desquamating HEAD, Eruption,
scales HEAD, Eruption, scrufy EXTREMITIES,
ankylosis, fingers, first joint of EXTREMITIES,
arthritis, nodosities EXTREMITIES, Eruption,
joints
152
EXTREMITIES, Eruption, elbow EXTREMITIES,
Eruption, elbow, psoriasis, patches EXTREMITIES,
Eruption, hand psoriasis, diffusa EXTREMITIES,
Eruption, hand, back of , psoriasis,
chronic EXTREMITIES, Eruption, hand, palm,
psoriasis EXTREMITIES, Eruption,, fingers,
psoriasis EXTREMITIES, Eruption, Knee,
psoriasis EXTREMITIES, Eruption, leg, psoriasis
153
SKIN, Eruption, desquamating SKIN, Eruption,
psoriasis SKIN, Eruption, psoriasis,
diffusa SKIN, Eruption, psoriasis,
inveterate SKIN, Eruption, psoriasis,
Syhpilitic SKIN, Eruption, psoriasis, red SKIN,
Eruption, psoriasis, scaly FACE, Eruption,
psoriasis of eyebrows GENETALIA MALE, Eruption,
scrotum, psoriasis
154
Grouping of symptoms of psoriasis in relation
with Miasms
PSORA Itching without pustules, Burning,
scaly.Eruptions recur annually. lt Winterlt During
sleep. gt Sunrise to sunset.gt Summer.gt Natural
discharges.gt Heat or warmth.gt Appearance of
suppressed eruptions.
155
SYCOSIS Unnaturally thickened skin.(Hyperkeratosis
)Increased exfoliation. Fish scaly eruptions.Nail
changes irregular, pitting thickened. lt Restlt
Damp, cold, rainy season.gt Wintergt Unnatural
discharges for mucosal surfaces. Joint pains
lt during cold, damp weather.gt Morning, dry
weather.
156
SYPHILIS Erythrodermic type.Tendency to fo for
ulcer with putrefaction. No itching, no
pain.Eruption slow to heal. Spoon shaped, paper
like thin nails with bending, tearing
easily. Periosteal and joint involvement. lt
Sunset to sunrise.lt Natural discharges.lt
Perspiration.lt Summer.lt Warmth of bed. gt Sunrise
to sunset.gt Warm climate.gt Unnatural discharges.
157

• 3. Aim Objectives
• Define the aims and objectives of the study.
• State whether nature of the problem has to be
  studied or solution has to be found by
  different methods.
• Primary
• Secondary

158
Example Psoriasis

• AIM AND OBJECTIVE
• Primary
• To observe the scope and efficacy of different
  homoeopathic medicines in the treatment of
  psoriasis.

159

• Secondary
• To find out the most suitable potencies.
• To determine the repetition schedules.
• To study the incidence of psoriasis in our
  hospital and relationship to age, sex,
  socioeconomic status, different occupation,
  habitats and other associated conditions.

160

• 4. Hypothesis-
• State your hypothesis.
• After the problem and purpose are clear and
  literature is reviewed.
• You have to start precisely with an assumption
  positive or negative, e.g. constitutional
  medicine is more effective for Lymphangitis
  than pathological prescription with
  Hydrocotyle Q.

161
Example Psoriasis
4. Hypothesis
It is a heredo- familial disease brought on by
stress, anxiety, mental trauma, fever, physical
injury etc on a genetic constitution.
Constitutional Homoeopathic medicine is to be
precsibed for its cure and it is hypothesized
that the cure rate can be augmented to 70-80
with above mode of treatment.
162

5. Plan of Action - Prepare an over all plan
or design of the investigation for studying the
problem and meeting the objectives.
163

• Definition of the population under study
• It may be country / state / districts / town /
  village / families / specific groups.
• Age group
• Income group
• Occupation
• Sexes
• Define clearly who are to be included and who are
  not to be included, i.e. (Inclusion and
  exclusion criteria)

164

• B) Selection of the sample
• It should be unbiased.
• Sufficiently large in size to represent
  population under study.

165

• Sample size
• - For Qualitative Data
• n4pq/L2
• Where p is the positive character, q 1-p and
  L allowable error, 10 or 20 of p
• - For Quantitative Data
• L2?/?n or ?n2?/L or n 4?2/L2

166

• Sample size for analytical studies
• Testing equality of two proportions ?1 ?2
• n Z 1-? ? 2?? (1 -??) - Z ? ? ?1 (1- ?1) ?2
  (1 - ?2) / ? 2
• Where ?? (?1 ?2) / 2
• b. Sample size for a case - control study
• c. Comparison of two population Means.
• n (Z1-? - Z?) ? / ? 2
• d. Comparison of more than two groups and methods

167

• b) Sampling methods
• Simple random sampling Choose random number
  from the table.
• ii) Stratified sampling - (Selecting 50 male
  50 female)
• iii) Systemic sampling - Systematically it is
  chosen.
• iv) Cluster sampling - Cluster may be identified
  (households) and random samples of cluster.
• v) Multistage sampling - In several stages.

168
Diagnostic Criteria

• Inclusion criteria
• Diagnosis of psoriasis is completely dependent
  upon the clinical findings.
• Typical distribution of lesion on scalp, elbow,
  knees, back and nails with well defined , non
  indurated dry silvery colored with layer upon
  scaling.
• Little or no itching.

169

• Auspitz sign, Candle-grease sign, Koebners
  phenomenon may be present.
• If after examination the skin, nails scalp,
  the diagnosis is in doubt, then skin biopsy may
  helpful for final confirmation.
• Family history of psoriasis.
• History of previous attack.

170

• Exclusion criteria
• Patients having other skin eruption, diabetes,
  tuberculosis, leprosy, seborrhoeic dermatitis,
  pityriasis rosea are not taken into
  consideration.
• After clear onset of the patient he / she
  will be selected for the clinical trial.

171

• Withdrawal Criteria
• If patient suffers from any other systemic
  disorder which requires immediate attention.
• If there is disease aggravation which requires
  immediate attention.

172
Sampling (a) Sample Size In view of the
design of this study. The sample size was set at
60 cases applying Formula L2?/?n or
?n2?/L or n 4?2/L2
173
Sampling Method Simple Random Sample method was
adopted Nature of Study Control
Study Blinding Single blind
174
Study of Instruments Following laboratory
tests were done. Skin biopsy ( In needed
cases) Hb DC ESR Stool Urine
175
Categorization of Patients
Group I. (Test group)
Group II (Control group)
176
Administration of Medicine - after
repertorisation
Choice of Potency - centesimal (30, 200, 1M)
50 millesimal potencies.
Repeated dose
Repetition Schedule
Single dose
Route of Administration of Medicines
Oral
177
Short description for Analysis of data
(A) Positive Responses
Mild Improvement
Marked improvement
Moderate Improvement
178

• Negative Responses
• No improvement, no response after sufficient
  period of time.
• Aggravation of signs and symptoms

179
For collection of data from various age
groups 0-10 11-20 21-30 31-40
180
For habitat It was made into two types
Rural
Urban
181
For occupation it was made into four types
Students Business person Unemployed House wives
182
For socio-economic status High Middle Low
183
For body built it was made into three types
Thin Moderate Obese
184
For collection of repetition schedule results
following parameter were fixed Single Dose
prescribed indicated drug (s) in single dose
and allowing patient wait for sufficient
period of time. Repeated Dose Indicated drugs
were administered daily.
185
OBSERVATIONS / PRESENTATION OF DATA
186
Table 1 Age wise distribution
187
Table 2 Sex wise distribution
188
TABLE 3 Habitat distribution
189
TABLE 4 Occupational distribution
190
TABLE 5 socio-economic status
191
TABLE 6 Distribution of psoriasis in relation
to season
192
TABLE 7 Distribution of psoriasis in relation
to body built
193
TABLE 8 INCIDENCE OF DISEASE
194
TABLE 9 Distribution of cases of psoriasis
depending on potency used
195
TABLE 10 RESULTS OF VARIOUS REPETITION
SCHEDULES
196
TABLE 11 FREQUENCY TABLE OF DRUGS OF CURED
CASES
197
TABLE 12 RESULTS OF DRUG RESPONSE
198
DISCUSSION
199
Age distribution
More prevalent in young age group (21 30)
Sex distribution
Male dominance (65.63)
Habitat distribution
More in Urban people (62.5)
Before treatment
200
Occupational variation
Unemployed patients and business persons are
mostly affected than others.
Socio-economic status
Prevalent in high class people
Seasonal variation
Highest in winter season and lowest incidence in
rainy season
After treatment
201
Body built variation
Obese people are more vulnerable
Relapses
1st time appearance cases are more than relapses
Distribution of various scales
Effectiveness of centesimal potency over
millesimal potency.
Before treatment
202
Repetition schedule
Single dose acts more perfectly than the repeated
doses.
Most effective drugs in the treatment
Graphites, Sulphur, petroleum, Thuja, Merc.
sol., Ars. Alb
After treatment
203
Drug response

• chi-square value is 21.8
• Table value is 3.81.
• Hence the null hypothesis is rejected and
• the result is significant.
• It is concluded that homoeopathic
• medicine is superior to placebo in
• treatment of psoriasis.

204
Before treatment
After treatment
CONCLUSION
205
Before treatment
After treatment

• Homeopathic medicine do act
• curatively for combating psoriasis.
• This validates the scientificity of
• Homeopathic cure observed by
• many expressed in various journals
• and periodicals.

206

• Medicines frequently occurring
• among the curative drugs are
• polychrest like
• Graphites
• Sulphur
• Petroleum
• Thuja occ.
• Merc. sol.
• Ars. alb.

After treatment
Before treatment
207
After treatment

• The therapeutic capabilities are
• dependent on mental generals,
• physical generals, characteristic
• particular, particulars and
• pathological symptoms too
• which constitute the Totality of
• symptoms

Before treatment
208
Thank you