ABC of Research Methodology

and Applied Biostatistics—

A Primer for Clinicians and
Researchers
 ABC of Research
Methodology and Applied
Biostatistics—A Primer for
Clinicians and Researchers
Mahendra N Parikh
MD, FICS, FICOG, FIMSA, FICMCH DA
Professor Emeritus, Nowrosjee Wadia Maternity Hospital, Mumbai
Editor Emeritus, The Journal of Obstetrics and
Gynecology of India
Consultant, Sushrusha Citizens’
Cooperative Hospital, Mumbai, India

Nithya Gogtay
MD, DNB (Pharmacology), DNB (Clinical Pharmacology)
Associate Editor, Journal of Postgraduate Medicine
Associate Professor, Department of Clinical Pharmacology
Seth GS Medical College and KEM Hospital, Mumbai, India

Forewords
S Arulkumaran
K Satyanarayana

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ABC of Research Methodology and Applied Biostatistics—
A Primer for Clinicians and Researchers
© 2009, Jaypee Brothers Medical Publishers
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First Edition: 2009
ISBN 978-81-8448-506-6
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 To

(Late Smt) Shobha M Parikh

 Foreword

Medical research outcome of today is clinical practice

tomorrow. Hence understanding research methodology is
vital for the researcher and essential for the clinician. The
ABC of Research Methodology and Applied Biostatistics –
A Primer for Clinicians and Researchers is an excellent book
for every clinician from beginners to those in established
practice. The fifteen chapters provide a wealth of information
and have been written in simple language. The chapters flow
from one to the other in a format and design that will help
the reader to understand research from “conception to
delivery”. It covers every aspect from the type of research
studies to planning ethics, execution, statistics, presentation
of manuscript and presentations to avoid pitfalls. The chapters
on misdeeds and misconduct and historical glimpses of
medical research provide interesting information.
I enjoyed reading the book cover to cover and admit that
I learnt a lot about medical research. I would highly
recommend it to all those involved in research and clinical
practice. The authors should be commended for a truly
valuable contribution to science.

S Arulkumaran
Professor and Head of Obstetrics and Gynaecology
St George’s University of London
 Foreword

The need for rigor in carrying out medical research that

could lead to better leads and strategies for the prevention,
diagnosis and management of disease is now beyond debate.
This is in fact a global call. But unlike basic biomedical
research with animals or in vitro systems, inherently endowed
with strong experimental methodology for reliability, medical
research has traditionally been handicapped to a large extent
due to the involvement of human subjects. Due to this and
other reasons, medical research is even accused of being
‘unscientific’ way of putting together evidences. Yet, medical
scientists have been braving along picking up nuggets of
new data, painstakingly analyzing and interpreting, generating
new knowledge that eventually finds way into practice. The
entire process of data-information-knowledge cycle has
undergone a sea change in the recent past. New evidences
are currently put to most stringent testing and evaluation
before applied in the clinic.
Considering the challenge, research culture among
medical scientists, especially from the clinical disciplines has
always been found wanting. One of our studies a few years
back showed that some medical colleges in India did not
publish a single paper in an indexed journal over a five year
period. So unlike other disciplines in science where the adage
is ‘publish and perish’ in medical research it has been more
of ‘publish or perish’. However, many who did publish
‘research papers’ could not transcend journals run by their
respective learned societies that did not particularly encourage
 x ABC OF RESEARCH METHODOLOGY

excellence. So, at a time when drastic revamp was called

for, our collective failure ensured perpetuation of mediocrity.
Even the hesitant and tentative hesitant steps were at best
ad-hoc.
But things seem to be looking up, albeit slowly, at least in
major cities like New Delhi, Mumbai, Chandigarh, if the
number of young doctors flocking the training workshops
on biomedical communication and research methodology is
any indication. A perceptible shift in the mind-set among
young and middle level medical professionals to learn - learn
the right (best) way of not just doing science but also publish
in the best international journals is visible. In the last three
years or so, even some journals published by learned societies
have changed, and for better. Evidence-based medicine is
slowly but steadily making its way into clinical practice.
Overall, the hunger for new knowledge that is on the rise,
augers well for the medical research establishment, patients,
and the country.
But the training to impart such skills has not been very
widely spread being limited by the handful of committed
individuals. The course material for most training workshops
on research methodology and biomedical communication is
largely borrowed from the west as several excellent books
written by eminent experts are available. Unsurprisingly, most
resource persons of workshops (being full time medical
teachers) find it convenient to liberally borrow from these
sources. Often, the content is not very appropriate to the
Indian participants, despite ‘Indianization’. A good resource
book on research methodology was always found wanting.
The ABC of Research Methodology and Applied Bio-
statistics: A Primer for Clinicians and Researchers, therefore,
 FOREWORD xi

is a very welcome addition. What is pleasantly surprising is

that the senior author Professor Mahendra Parikh is an
obstetrician and gynaecologist by training, a discipline not
exactly in forefront of medical research in India. Dr Parikh’s
passionate commitment to promote medical research, build
skills and empower young medical researchers is evident by
the widely attended workshops organized in various parts of
India. Under his leadership, the Journal of Obstetrics and
Gynecology of India has been running the very successful
PICSEP (Program for Inculcating the Culture of Scientific
Enquiry and Pursuit) Project since 2003. Co-authored with
a young promising clinical pharmacologist Dr Nithya Gogtay,
this booklet gives the elements of research methodology and
biostatistics from a practitioners’ point of view. Written in a
very simple and easily understandable way (especially medical
statistics), the booklet contains little of everything a young
researcher should know – planning and designing a study,
execution publication of a research paper, evidence-based
medicine, application of biostatistics, ethics, research,
misconduct etc.
I hope this is only the appetizer and Drs Parikh and Gogtay
will dish out a comprehensive resource book in the not too
distant future.

K Satyanarayana
Editor, IJMR
 Preface

Progress in every walk of human activity depends upon

research based on new ideas. So it is in the field of medicine
too. Medical students are exposed to epidemiological research
while studying Preventive and Social Medicine. During
undergraduate days, they have opportunities to learn Research
Methodology if they wish to. But during postgraduate training
they must learn Research Methodology while working on
and writing their thesis or dissertation which is an essential
and integral part of the postgraduate examination.
Unfortunately, thesis writing is often not taken seriously and
considered a mere formality at a vast majority of universities
in the developing countries. The current scientific methods
of conducting research developed over the past six decades,
have been refined only in the last 30 years. Even the Heads
of Departments in many medical colleges are ignorant of
these new methods. As a result, most published research is
poorly done and there is a great need to improve the quality
of research done especially in developing countries.
The Senior Author became Editor of the Journal of
Obstetrics and Gynecology of India in 2003 after working
in many editorial positions for three decades and having a
vast teaching experience. He soon realized the need for training
postgraduate students and teaching staff in Research
Methodology. Hence, he initiated the project designated as
Program for Inculcating the Culture of Scientific Enquiry
and Pursuit (PICSEP). The project has expanded in many
different directions and is showing good results benefiting
 xiv ABC OF RESEARCH METHODOLOGY

students, teachers and clinicians. Clinicians must become

knowledgeable about the basics of Research Methodology
including the basis of Applied Biostatistics to be able to
evaluate the medical literature they read. The junior author is
regularly conducting training programs of 12 half-day
sessions for undergraduate and postgraduate medical students
since 2003 besides being part of the editorial team of the
Journal of Postgraduate Medicine and Journal of Association
of Physicians of India for a decade. During these activities
involving training hundreds of researchers and clinicians,
we realized a great need for a simple, compact and compre-
hensive book on this subject, written in plain language, devoid
of scientific jargon and directed at clinicians and research
workers. Most western books are beyond the reach of readers
in developing countries due to their prohibitive cost and
complexity of writing.
This book is written keeping in mind the needs of
undergraduate and postgraduate students and their teachers,
junior researchers and their guides and the clinicians. The
clinicians are consumers of research since they utilize it in
their day-to-day practice.
It is hoped that the book will in a small way contribute to
improving the quality of research done in developing countries
and empower the clinicians to evaluate the quality of research
that they read in journals and listen to in conferences.
Suggestions and comments from the readers are most
welcome.

Mahendra N Parikh
Nithya Gogtay
 Contents

1. Introduction ............................................................. 1
What is research? ...................................................... 2
Why do we do research? .......................................... 2
Choosing a topic for research ................................. 4
2. Types of Research Studies .................................... 7
Types .......................................................................... 8
Case control studies .................................................. 9
Cohort studies ........................................................... 9
Cross sectional studies ............................................ 10
Randomized controlled trial ................................... 10
Large simple clinical trials .................................... 19
Descriptive studies .................................................. 19
Diagnostic tests ....................................................... 20
Meta-analysis........................................................... 22
Multicentric trials ................................................... 23
New drug development – Phase I to IV studies .. 24
3. Planning and Design of a Study ........................ 25
Hypothesis testing ................................................... 26
Study subjects or participants and recruitment,
inclusion, exclusion criteria ................................... 27
Statistical errors ...................................................... 28
Power of a study .................................................... 29
Sample size calculations ......................................... 30
Interventions ............................................................ 30
Bias and confounders ............................................. 30
xvi ABC OF RESEARCH METHODOLOGY

End points ............................................................... 32

Follow up ................................................................ 34
Data collection and data management ................. 35
Statistical evaluation of data ................................ 37
Funding .................................................................... 37
4. Ethics in Research................................................ 41
Evolution of ethics ................................................. 42
Participants’ rights .................................................. 42
Ethics committees .................................................... 42
Ethics committee approval ..................................... 43
5. Applied Biostatistics ............................................. 45
Indispensability of statistics ................................... 46
How much statistics does a clinician need to
know? ....................................................................... 47
Population, sample and sample size ..................... 48
Probability and odds .............................................. 50
Mean, median, mode .............................................. 51
Normal distribution ................................................. 51
Standard deviation, variance and standard
error of mean .......................................................... 54
Percentiles and quartiles ........................................ 55
P value .................................................................... 56
Confidence intervals ............................................... 56
Measures of association—Association between two
events, relative risk, risk ratio and odds ratio .... 58
Risk measurements .................................................. 60
Correlation and correlation coefficient ................. 62
Regression analysis ................................................. 64
Survival analysis ..................................................... 66
 CONTENTS xvii

Choosing an appropriate statistical test................ 70

Role of biostatistician ............................................ 70
6. Submitting a Paper for Publication .................. 75
Choosing the journal .............................................. 76
Submitting a research paper for publication ........ 76
The anatomy or structure of a scientific paper ... 77
Submission of rejected paper to another
journal ...................................................................... 83
Additional points ..................................................... 83
Writing a case report .............................................. 84
7. Evidence Based Medicine (EBM) ....................... 87
Importance of EBM................................................ 88
Sources of evidence ................................................ 88
Evidence of efficiency as well as of safety ......... 91
Science of reading a journal and evaluating
evidence ................................................................... 92
Levels of evidence .................................................. 94
8. Presenting Papers at Meetings and
Conferences ........................................................... 97
9. Misdeeds and Misconduct in Research and
Publication ............................................................ 101
Misdeeds and misconduct ..................................... 102
Prevention of misconduct ..................................... 104
10. Registry of Clinical Trials ................................. 105
Registry .................................................................. 106
Registration of a study ........................................ 107
11. Good Clinical Practice (GCP) and Good
Manufacturing Practice (GMP) ........................ 109
xviii ABC OF RESEARCH METHODOLOGY

12. Historical Glimpses of Research in

Medicine .................................................................113
Evolution of research methods.............................. 114
Evolution of ethics in research ............................. 117
13. Abbreviations ........................................................ 119
14. Demystification of Technical Jargon ............... 123
15. Bibliography ......................................................... 131

Index ...................................................................... 133