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Research & Statistics

for MRCPCH Exam

ELBA
BA
Topics
Making a Study
Medical Statistics
Critical appraisal
Clinical governance
Modern way to deliver best medical care to the
patients.
Shared responsibility of all health professionals
to provide optimal care to the patients in a way
that they would like to be treated themselves.
It consist of 9 components:
3 Health professionals
3 Patients
3 Medical care system
Health professionals
1. CME
2. Team work
3. Risk management
Patients
1. Advice cards
2. Good communication
3. Access to complains
Medical care system
1. EBM
2. Audit
3. Updated guidelines
Medical
care
system
Guidelines
Guidelines
1. Juniors
2. EBM
3. NICE
4. Updated
5. Changeable
AUDIT
Audit chain
Audit
Is a process by which health professional
assess, evaluate and improve the care of
patients in a systematic way.
It is best summarized by a circle or chain
process.
Standard

Problem Data

Change Method
Results
EBM
EBM
1. Formulation of question
2. Search for evidence
3. Critical appraisal
4. Applying of evidence
5. Evaluation of effect
Formulation of question
1. Population
2. Intervention
3. Comparison !!
PICO
4. Outcome
Recommendation grades
and levels of evidence

From A to E
A
At least one high quality meta-
analysis, systematic review of
RCTs, or RCT with a very low risk
of bias, and directly applicable to
the target population.
B
A body of evidence including well conducted
casecontrol or cohort studies with a low
risk of confounding, bias, or chance and a
moderate probability that the relationship
is causal, directly applicable to the target
population, and demonstrating overall
consistency of results.
C
A body of evidence including well conducted
casecontrol or cohort studies with a low
risk of confounding, bias, or chance and a
moderate probability that the relationship
is causal, directly applicable to the target
population and demonstrating overall
consistency of results.
D
Non-analytic studiesfor example,
case reports, case series, or
expert opinion.
E
No evidence exists; recommended
best practice based on the clinical
experience of the guideline
development group.
Study
Research Study

Is an organized project to analyze a specific problem.


This project is almost always use a statistical analysis
This reflects the essential need for understanding at
least the basic statistical methods to do or critically
appraise the project
Delivery of a Research study

1. Idea
2. Question
3. Search
4. Design
Milestones of a Research study

1. Contact the research department early


2. Study plan
3. Set the study design and type
4. Estimate the Power calculation
5. Study process
6. Publication
7. Critical Appraisal
Steps of a Research study
The plan
Time, Place & Population (Sample)
Team
Fund
Ethics
EthicalCommittee
Patient permission
STUDY DESIGN

1. Question & Population Title & Aim of the work


2. Background information Introduction
3. Sample
4. Data collection Method
5. Statistical analysis
6. Outcome Results
7. Compare the results Discussion
8. Answer the question Conclusion
9. Advices for future Recommendation
10. Sources References
Population Sample
1. Size
2. Power see later
3. Inclusion & Exclusion
To minimize the errors
1. Randomization Simple or stratified
2. Matching
3. Blindness
4. Allocation concealment
Needed when intervention is complex and cant be blinded

5. Intention to treat analysis


Consider initial allocation in case of loss May be the
intervention is the reason
Randomization
Simple
Using computers or other methods less commonlty
Stratified
Best used for rare disorder and multicenters study or when
the outcome can be affected by the severity of illness
Errors
Random effect of chance
Minimized by increase sample size to narrow the CI
Systematic Bias
Minimized by well study design

Bias
1. Selection
2. Measurement e.g. Recall Bias
3. Confounding
Confounding Factors
Major:
Controlled by well study design
Minor:
Controlled by Logistic regression analysis
Unknown:
Remains unknown until detected by other study
Case Control study
Retrospective study
Two groups
Control group
Determine the causation (Past exposure)
Suitable for rare disease
t-test for parametric Example:
Odds ratio CRF in Bartter Syndrome
Note: Case report or case series is completely different
Cohort study
Mainly Prospective study
Use recall if retrospective
Two groups
Control group
t-test for parametric
Evaluate the risk (Future exposure) or incidence
Suitable for common disease
Relative Risk (RR)
Example:
Hypertension in Obesity
Cross sectional study

Present time
Evaluate the disease frequency or
risk factor
Diagnosis & prevalence

Example:
Incidence of Familial short stature
Cross over study
Each individual exposed to each arm
To see which intervention is better
Needs wash out period in-between
Evaluate the short term effect of intervention
Suitable for relatively stable chronic disease

Example:
ACEI Vs Ca channel blocker in renal hypertension
Pilot study
One of Prospective study
Small sample size
No control group

Example:
Deafness after bacterial meningitis
Randomized Control Trial
Intervention
Two or more groups
Needs control group
Placebo
Example:
Randomization
Pantoprazole in GORD in infancy
Blindness
Efficacy (Statistically)
Effectiveness (Clinically)
Meta-analysis
Different studies with
similar subject (Usually
RCT)
Pooled result on a graph
Log scale or Frost plot
Expressed as Odds ratio
or Relative Risk
Meta-analysis is the
statistical method used
in Systematic review

Example:
Steroid in Bronchiolitis Systematic review is NOT a review article
Conclusion of study type
Case control: Effect of multiple risk factors on rare
outcome
Cohort : Rare risk factor on multiple outcome
Cross sectional: for incidence and prevalence
RCT: Assessment of intervention effectiveness
Statistics
Medical statistics
Statistics
Definition: Measurement of chance.
Studying population sample to give idea about
all population (Distribution)
Quantify the degree of difference between 2 or
more groups of variables (tests of significance)
Ensure that research results are comparable and
can be generalized (Appraisal)
Statistics
1. Measures of Distribution
2. Measures of Central tendency
3. Measures of Dispersion
4. Measures of Probability
5. Measures of Effect
1. Distribution
1.Normal Gaussian :Most of variable
2.Skewed: Trend to either extreme
3.Binomial: Two possible outcome only
4.Poisson: Rare event in large population
1. Distribution
(Screening tests)
Simple Confirmatory test
Cheap Total
Screening + ve - ve
Reliable
A B AB
Applicable + ve
Serious illness C D CD
- ve
Intervention available
Total AC BD ABCD

1. Incidence: New cases within a specific period of time


2. Prevalence: Present cases AC/ABCD
3. Sensitivity: +ve for confirmatory test A/AC
4. Specificity: -ve for confirmatory test D/BD
5. Positive predictive value: +ve for Screening test A/AB
6. Negative predictive value: -ve for Screening test D/CD
1. Distribution
(Screening tests)
Confirmatory test
Simple
Cheap Screening Total
+ ve - ve
Reliable
A B AB
Applicable + ve
Serious illness - ve C D CD
Intervention available
Total AC BD ABCD

7. Likelihood ratio for positive result: sensitivity/1-specificity


8. Likelihood ratio for negative result: 1-sensitivity/specificity
9. Yield of the test: A/ABCD
Pre-test Odds = Prevalence / (1- Prevalence)
Post-test Odds = pre-test Odds x LR
Confirmatory test

Example Screening + ve
80
- ve
20
Total

100
+ ve
- ve 40 160 200

1. Incidence = Total 120 180 300

2. Prevalence =
3. Sensitivity =
4. Specificity =
5. Positive predictive value =
6. Negative predictive value =
7. Likelihood ratio for positive result =
8. Likelihood ratio for negative result =
9. Yield of the test =
pre-test Odds =
post-test Odds =
Confirmatory test

Example Screening + ve
80
- ve
20
Total

100
+ ve
- ve 40 160 200

1. Incidence: ?? Total 120 180 300

2. Prevalence: 120/300 = 0.40 = 40%


3. Sensitivity: 80/120 = 0.66 -= 66%
4. Specificity: 160/180 = 0.88 = 88%
5. Positive predictive value: 80/100 = 0.80 = 80%
6. Negative predictive value: 160/200 = 0.80 = 80%
7. Likelihood ratio for positive result: 0.66/1-0.88 = 5.5
8. Likelihood ratio for negative result: 1-0.66/0.88 = 0.38
9. Yield of the test: 80/300 = 0.26 = 26%
pre-test Odds = 0.40 / (1- 0.40) = 0.66
post-test Odds = 0.66 X 5.5 = 3.6 OR 0.66 X 0.38 = 0.25
2. Central tendency
1. Rank
2. Mean Arithmetic or geometric
3. Mode
4. Median
Mean = V/n0
1 SD = 68%
2 SD = 95%
3 SD = 98%
1.96 SD = 95%
3. Dispersion
1. Range
2. Percentile
3. Quartile
4. Variance (V-mean )2/n0
5. SD: Variance
6. Coefficient of variation SD/Mean x 100
7. SEM: SD/n0
8. CI: Mean K x SEM K=1.96 CI = 95%
Example
A class of 100 students you are studying the
height among them
Number = 100
Mean = 120 cm
Variance = 100
SD = ?
?? % of student 110-130 cm
Coefficient of variation = ??
SEM = ??
95% CI = ??
Example
A class of 100 students you are studying the
height among them
Number = 100
Mean = 120 cm
Variance = 100
SD = 10
68% of student 110-130 cm
Coefficient of variation = 8.3%
SEM = 1
95% CI = 118 122 cm
4. Probability
Null hypothesis H0 : In reality no difference
P-value : The probability of observed result has
arisen by chance. P-value 0.05 = the probable
chance is only 5%
Confidence interval: With 100 times study
repeat the probability of all results will be within the
interval. 95% CI = 5% chance the result will be
outside range.
The wider the range the greater uncertainty. Can be used with mean, RR, OR,
Fact of Power Calculation
Is a statistical method used to calculate the
appropriate sample size for the study to ensure
that any difference is statistically significant
(Reject Null hypothesis H0)
Calculated as (1- error)
Good power is > 80-90 %
The power is dependant on:
Sample size
Significance level
Power of the study
Study power is how likely p-value your study
will find a statistically significant difference
between two groups, if it is actually present.
Epidemiologists estimate the incidence rate for
each group when calculating the study power.
Only by increasing the sample size can a simultaneous
reduction in both and be achieved.
The probability, 1 , of detecting a specified difference, ,
is called the power of the study.
How is Study Power Calculated?
The following items are put into a formula calculating study power:
1. Sample size
The total number of people in the study. Researchers base this estimate
on the proposed study design, and the total number of exposed people.
2. Estimate of disease rate for unexposed population Control
Researchers base this estimate on what is currently known about the
presence and patterns of that disease in human populations.
3. Estimate of disease rate for exposed population Patients
Similar to the previous item, researchers use current knowledge to
estimate this rate. Researchers may also conduct a pilot study to gather
data to make this estimate.
4. Level of significance
Before conducting the study, researchers choose the level of
significance, which is the p-value they would like to achieve in their
study. Researchers commonly set the level of significance at 5% or less.
Blank
software
Example
4. Probability
1. Tests of significance
2. Correlation
Non-Parametric
3. Regression 2 or more groups
Not normally distributed
Qualitative variables
Parametric 1. Chi square (X2) test
2 groups (Means) 2. Wilcoxon rank test
Normally distributed 3. Mann-Whitney test
Quantitative data 4. Kruskal-Wallis test
1. t-test (paired/unpaired) 5. Spearmans rank correlation
2. Pearson correlation
4. Probability
1. Tests of significance
2. Correlation
3. Regression

t-test Null hypothesis


1. Means diff./ SEM diff. P value: 0-1
2. Critical (t) value Type I error:
3. df = n-1 Paired Type II error:
4. df = (n1-1)+(n2-1) Unpaired
5. P value can be calculated
Power: 1- x100
CI: 95%
2
X (chi-squared) test for 2 X 2
tables

2 X 2 table
Pearsons Correlation
Parametric
Linear correlation
r value -1 to +1
Closer to zero = less correlation
Closer to 1 = stronger correlation

Regression
1. Multiple linear regression
2. Logistic regression

Regression
Multiple linear regression
Formula Y= a + b X
(Regression coefficient)
A is Y value when X is zero
B is the degree of sloping of the line to the baseline
Logistic Regression
Used when the dependent variable response is binary Two possible
outcome .
Comparing these outcome with one or many independent variables
By fitting the data to Logistic S-shaped curve

The output is confined to values between 0 and 1. 0 - 100%


Probability can be estimated from the curve. P-value <0.05
Best to compare the odds ratios in case control study
Help in correction of multiple potential confounding factors
5. Effect
Absolute risk (AR): A/A+B (Cohort) # of cases / # of Total
Relative risk (RR): A/A+B/C/C+D (Cohort)
AR Reduction: Like AR but in control group D/CD
RRR: Like RR but in control group reversed (1-RR)X100
Number needed to treat (NNT): 1/RRR How many to ttt. to prevent one
Odds ratio: AC/BD (Case control) #of cases / #of non-cases
Diseased Non Total

A B AB
Exposed
C D CD
Non
Total AC BD ABCD
Diseased Non Total

60 40 100
Exposed
Example
20 80 100
Non
Total 80 120 200

Absolute risk = ??
Relative risk = ??
AR Reduction= ??
RRR= ??
Number needed to treat = ??
Odds ratio= ??
Diseased Non Total

60 40 100
Exposed
Example
20 80 100
Non
Total 80 120 200

Absolute risk = 60/100 = 0.6 A/A+B


Relative risk = 60/100/20/100 = 2.3 A/A+B/C/C+D= AD/BC
AR Reduction= 80/100 = 0.8 D/CD
RRR= 1-2.3X100= -200 (1-RR)X100
Number needed to treat = 1/-200 = 0.005 1/RRR
Odds ratio= 80/120 = 0.66 AC/BD
Relative Risk Vs Odds Ratio
Relative Risk: If 2x2 data is from a cohort study (prospective),
then use the Relative Risk value which is the ratio of the rate
of events in the control (unexposed) group A/A+B" to the rate
of events in the experimental (exposed) group C/C+D".

Odds Ratio: If 2x2 data is from a case-control study, then use


the Odds Ratio value which is the ratio of the odds of disease
for the experimental group over the odds of disease for the
control group. Or the ratio of the odds of being exposed or
unexposed in the "case" group A/C" to the odds of being
exposed or unexposed the "control" group B/D".
Odds ratio & Relative risk
< 1 .. The intervention is effective
> 1 .. The intervention is harmful
= 1 .. The intervention is
ineffective
Critical
Appraisal
Critical appraisal of an
article
1. Validity
Can I believe the study? Design
2. Perfection
Is the result are really important? Method
3. Applicability
Can I implement the study to my patient?
1. Population 2. Benefit over risk 3. Accessibility
Check
Critical appraisal of an article / Validity
Focused question
Clinical relevance of the question
Subjects with similar characters
Inclusion & Exclusion criteria
Randomization
Blinded state
Subject entered reaches the end
Statistical methods are appropriate
Critical appraisal of an article / Perfection

Size of treatment effect (Power of the study)


Precision of the results (Confidence interval)
Confounding factors? (Logistic regression)
Statistical sig. Vs Clinical relevance (Efficacy
vs Effectiveness)
Critical appraisal of an article/ Applicability

Our patients have a similar characters


All clinically important outcomes were measured
Change my practice
Any obstacle to apply it
References
Using and Understanding Medical Statistics 2007
Essential revision notes for MRCPCH 2006
Basic sciences for MRCP 2005
Wikipedia last modified on 4 June 2010
Master Course for MRCPCH 2007
THE
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