study material

1. Ins and OUTs

2.  Types
 Level of evidence
 Randamization
 Designs
 Statistical tests used
 Advanced statistical tests
 Critical appraisal
 Critical appraisal tools
 Clinical trial design issues

3. Types
 Types of trials
 Randomised clinical trials (RCTs)
 Non- Randomised clinical trials-Allocation to the
different treatment groups of a trial is not done
through proper randomization process

4. Level of evidenceFive levels of evidence
Level Research Design Description
Level 1
Randomized controlled
trial (RCT)
Randomized controlled trial, PEDro score 6. Includes within
subjects comparison with randomized conditions and cross-over
designs
Level 2
RCT Randomized controlled trial, PEDro score < 6.
Prospective controlled trial Prospective controlled trial (not randomized)
Cohort
Prospective longitudinal study using at least 2 similar groups with
one exposed to a particular condition.
Level 3 Case control
A retrospective study comparing conditions, including historical
controls
Level 4
Pre-post
A prospective trial with a baseline measure, intervention, and a
post-test using a single group of subjects.
Post-test
A prospective post-test with two or more groups (intervention
followed by post-test and no re-test or baseline measurement) using
a single group of subjects.
Case Series
A retrospective study usually collecting variables from a chart
review.
Level 5
Observational Study using cross-sectional analysis to interpret relations.
Clinical Consensus
Expert opinion without explicit critical appraisal, or based on
physiology, biomechanics or "first principles"
Case Report Pre-post or case series involving one subject
Editors: Riegelman, Richard K.Title: Studying a Study & Testing a Test: How to
Read the Medical Evidence, 5th Edition, 2005, Lippincott Williams & Wilkins

5. Randamization
 Methods of Randomization
 1. Fixed Randomization Methods
 Simple randomization-tossing coin, random number
tables or computer generated random numbers
 Block randomization
 Stratified randomization
 Randomized consent method
 2.Adaptive Randomization Methods
 Play the winner
 Minimization

6. Non randomization
 Alternate allocation
 Geographical distribution
 Cluster allocation
 Odd/even number allocation
 Based on date of birth/surnames /alphabetical orders

7. Designs
 RCT designs
 1. Factorial design
 2. Cross- over design
 3. Cluster random design
 4. n-of-1 trials
 5. Open trials

8. Statistical tests used
 Parametric and non parametric tests
 ANOVA

9. Statistical tests used
Nonparametric Tests Parametric Tests
 Chi-Square test- For frequency data
 Fisher’s exact test.
For N x N design and very small
sample size Fisher's exact test should be applied
 McNemar test
McNemar test can be used with two
dichotomous measures on the same subjects
(repeated measurements). It is used to measure
change.
 Mann-Whitney test -Ordinal data
independent groups.
 Wilcoxon signed rank test- Ordinal data
dependent (paired samples)groups
 Kruskal-Wallis test -Ordinal data
independent groups (more than 2 groups)
 Friedman test- Ordinal data repeated
measures.
 Measures of association.
Spearman correlation coefficient- for
correlation of non -parametric data.
 One group t-test - Comparison of
sample mean with a population mean.
 Independent groups t-test- Comparison
of means from two unrelated groups
 Dependent or paired t-test- Comparison
of means from two related samples
 k unrelated group, one -way ANOVA
test, two way ANOVA test- Comparison
of means from k unrelated
groups(more than 2 groups)
 Repeated measures ANOVA- Interval or
ratio data repeated measures
(Comparison of means from k related
groups)
 Measures of Association.
Pearson correlation coefficient- for
correlation of parametric data

10. Parametric tests and analogous nonparametric procedures
Type of analysis Example Parametric tests Nonparametric tests
Compare means between
two independent groups
Is the mean Quality of life score of
incontinence patients (at baseline)
for patients assigned to placebo
different from the mean for
patients assigned to the treatment
(Interferential therapy) group?
Two-sample t-
test
Wilcoxon rank-sum
test
Compare two quantitative
repeated measurements
taken from the same
sample
Was there a significant change in
Quality of life score of incontinence
patients between baseline and the
Four-month follow-up
measurement in the treatment
group?
Paired t-test Wilcoxon signed-rank
test
Compare means between
three or more
independent groups
If the study have three groups (e.g.,
placebo, Interferential therapy,
kegal’s exercises),to know the mean
difference among the three groups?
Analysis of
variance
(ANOVA)
Kruskal-Wallis test
Association between two
quantitative variables
Is Quality of life score associated
with the patient’s age?
Pearson
coefficient of
correlation
Spearman’s rank
correlation

11. Advanced statistical tests
 Relative risk
 Relative risk reduction
 Relative risk increase
 Absolute risk reduction
 Absolute risk increase
 Number needed to treat
 Number needed to harm
 Risk-benefit analysis

12. Critical appraisal
 Strength and weakness/issues of
RCT designs
 Sample size calculation stated in the
study
 Selection methods- randomization
in allocation -handles the issue of
confounding factors of the study
 Selection bias –inclusion and
exclusion criteria
 Homogenous groups are compared-
no distribution bias
 Blinding – reduces the bias of
experimenter observation
 Performance bias- groups treated
equally apart from the treatments.
 Standardized procedures followed
in administering the treatment
protocols
 Reliability and validity of outcome
measures used.
 Duration of the study – adequate
follow up logically needed to find a
difference.
 Intention to treat analysis
performed- whether subjects
received or completed the
treatment.
 Drop outs management.
Worst case scenario method.
Last data carried forward method
 Appropriate statistical tests

13. Critical appraisal tools
 Appraisal of a meta-analysis or systematic review
 Appraisal of a controlled study
 Appraisal of a cohort or panel study
 Appraisal of a case control study
 Appraisal of a cross-sectional study (survey)
 Appraisal of a qualitative study
 Appraisal of a case study
 Checklist for Analytical Cross Sectional Studies
 Checklist for Quasi-Experimental Studies (non-
randomized experimental studies)
 Checklist for Prevalence Studies

14. Critical appraisal tools
 AGREE - http://www.agreecollaboration.org/
 Alberta University Evidence Based Medicine Toolkit - http://www.ebm.med.ualberta.ca/
 CASP - http://www.sph.nhs.uk/what-we-do/public-health-workforce/resources/critical-
appraisals-skills-programme
 CATwalk - http://www.library.ualberta.ca/subject/healthsciences/catwalk/index.cfm
 CEBMH - http://cebmh.warne.ox.ac.uk/cebmh/education_critical_appraisal.htm
 Centre for Evidence Based Medicine - http://www.cebm.net
 CLIST Resources for Critical Appraisal - http://www.londonlinks.nhs.uk/groups/clinical-
librarians-informationskills-trainers-group/trainers-toolkit/resources-for-critical-
appraisal
 Scottish Intercollegiate Guidelines Network (SIGN): • http://www.sign.ac.uk/
 AMSTAR • Shea, B.J., Grimshaw, J.M., Wells, G.A., Boers, M., Andersson, N., Hamel, C., &
Bouter, L.M. (2007). Development of AMSTAR: A measurement tool to assess the
methodological quality of systematic reviews. BMC Medical Research Methodology,
7(10). doi: 10.1186/1471-2288-7-10 • Article link: http://www.biomedcentral. com/1471-
2288/7/10

15. Clinical trial design issues
 Appropriate statistical tests (e.g.;-pre-post design
analysis ‘T’ test Vs Anova)
 Surrogate end points –Information bias
 Hawthorne effect( handled by keeping a silent group)
 Interim analyses( to avoid abundant sample coverage)
 Drop outs management.
 Worst case scenario method.
 Last data carried forward method