Biomedical Research Methodology Ranjan Das, PN Das
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FM1Biomedical Research MethodologyFM2
FM3Biomedical Research Methodology: Including Biostatistical Applications
Ranjan Das MBBS MD (Community Medicine) Postgraduate Certificate in Hospital Management (NIHFW) Certificate in Epidemiology (NICD) Professor Department of Community Medicine Lady Hardinge Medical College and Associated Hospitals, New Delhi, India Formerly Lecturer at Jawaharlal Nehru Medical College Aligarh Muslim University, Aligarh and Santosh Medical College, Ghaziabad Assistant Controller of Examinations National Board of Examinations (NBE) New Delhi, India PN Das MBBS Diploma MCH Lecturer cum Medical Officer Delhi Institute of Rural Development New Delhi, India Foreword AK Sood
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Biomedical Research Methodology
© 2010, Jaypee Brothers Medical Publishers (P) Ltd.
All rights reserved. No part of this publication should be reproduced, stored in a retrieval system, or transmitted in any form or by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the authors and the publisher.
First Edition: 2010
9789350250174
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FM5
To
Our parents and studentsFM6
FM7Preface
Pasteur said in the field of research, chance favors only the prepared mind. It has to be accepted that the seeds of great discovery are constantly floating around us, but they take roots only in the minds of those well-prepared to receive them. This is true for the fields of medicine, biology, and sociobehavioral sciences too, which all fall under the domain of biomedical research. Knowledge generated form research in these areas has a crucial role in the betterment of medical and health practices. Yet unfortunately, research has never got its rightful place in biomedical academics. So much so, there is no chapter in the undergraduate curriculum of medicine that is devoted to research, what to speak of it as an independent subject. Besides, training for research is also a neglected arena in the biomedical field. Research methodology, as a subject, is taught probably only in one postgraduate curriculum in the whole of Medical Sciences (i.e. Public Health) where it constitutes just about 5% of the overall curriculum. Lack of training in biomedical research, leads to a shortage of competent researchers; this in turn hinders research and the benefits that would have accrued to the society at large.
Research, today is truly an international activity, and researchers from different nations are contributing to the pool of science for the benefit of mankind. It is for this reason that policy-makers at the national and international level would like to see more of research. In the absence of trained, if not qualified researchers, all countries—developed as well as developing are going to be affected. The Global Forum for Health Research (2001) reported that the global investment in health research stood at an estimated US$ 75 billion. The share of investment was as follows: 47% from governments in developed countries, 42% from the pharmaceutical industry, 8% from the private not-for-profit sector, and 3% from governments in developing countries. It also noted that funding has never been more available for health research than it is today. Yet a word of caution must be added: that these 75 billion US$ would not be sufficient to put newer strategies and action, and at the pace they are needed. That is simply because it constitutes only 3.4% of the world health expenditures.
Research accounts for about 13% share of overall sales revenues of major pharmaceutical companies worldwide. It has been the tradition of pharmaceutical companies in the past to do most of their research in-house. Nowadays, a growing number of pharmaceutical companies commission their research to reputable centers in universities. Many companies today outsource more than 30% of their research and development budget and all or part of their clinical research.FM8
For all these reasons, building a career in biomedical research is certainly worth a proposition. According to a McKinsey report (2007) biomedical researchers are going to be in great demand worldwide; 250,000 would be needed worldwide and 50,000 in India alone. Yet, only few institutes cater to this need and produce only a fraction of the numbers needed. In monetary terms also, the biomedical research industry is growing at an unprecedented pace of 30-40% each year (McKinsey Report).
Further, there is little doubt that biomedical research now demands high levels of expertise in all the above mentioned domains and many more. Yet, for the debutant biomedical researcher, finding help from so many professionals may be an extremely challenging task if not a dream. It is, therefore, pertinent that all professionals from the biomedical field, and especially doctors, more so those at the postgraduate level have some understanding of research methodology. Even if we do away with all other areas, three would continue to form the core of biomedical research, namely, epidemiology, biostatistics and sociology. Though most students of the medical sciences have had a brush with all these three, yet the depth of it is not sufficient for it to be applied to research. In context of the other fields of biomedicine, some fields lead to a better knowledge of biostatistics and others sociology, though epidemiology is an area which has generally been left untouched.
Over the years, we have seen our postgraduate students struggle with their research project and thesis. To us nothing has been more satisfying than helping our students understand difficult concepts and enabling them to put those to use. That prompted us to do our bit to help them by documenting our experiences in a book. Even at the time when we were ourselves enrolled for postgraduate level research, we had searched for a short book on the techniques to be used for biomedical research. However, our search had proved futile then, and even now, nearly 20 years down the line there is probably not one title that can be used by entry-level researchers to guide them in their debut research work. With the above ideas in mind we thought of writing this book, the primary audience of which is the postgraduate student of medical, dental, nursing and allied specialties. These young professionals have to plan and execute a research project and submit the thesis to be eligible for appearing in their university examinations. Needless to say, this book should also serve as a valuable resource book for others already working in the field of biomedical research.
The content of the text of is based on our own experiences as well as on the inputs received from our colleagues and inquisitive postgraduate students. The chapters have been ordered in a way to assist student researchers overcome the barriers they encounter, while conducting the research. We believe this book would prove to be highly resourceful in dealing with the practicalities of research, beginning from the very preliminary stages, through literature review, data analysis, right up to the final stage of writing the thesis and even getting the message out by publication.FM9
Our whole hearted efforts for writing this book shall be successful only if it really benefits the target audience, and that shall be our reward as well. It spite of our best efforts, many errors might be there in the text. We shall be highly grateful and remain obliged to our esteemed readers for pointing out those to us. Constructive criticism on the content and its presentation is extremely necessary for the improvement of any work, and we welcome them for enriching our knowledge as well as for improvement of the book. Substantial contributors of these would certainly be credited through acknowledgment, if not anything more.
Ranjan Das
PN Das
FM11Foreword
It gives me immense pleasure and satisfaction to write the foreword for Biomedical Research Methodology. There are two reasons for it. Firstly, because very few books are available on this extremely important subject. Secondly, Dr Ranjan Das is a teacher whom students hold in high esteem.
Research is a very important tool in the hands of biomedical professionals, and it has been and would continue to be a major force in this field. Most of the medical fraternity consists of clinicians, and they apply a wide array of scientific principles, strategies and tactics called research to answer questions about disease, health and health care. Such is the importance of research that all postgraduates in the biomedical field have to undertake a research project and submit a thesis. However, unfortunately, research methodology is taught neither at the UG level nor at the PG level. Worst still, there is an extreme paucity of concise yet comprehensive texts, suitable for use by first time researchers in the biomedical field.
Dr Ranjan Das and his collaborators need to be congratulated for their bold effort. I hope Biomedical Research Methodology would prove to be of immense help for biomedical researchers at any stage of their career, beginning from the student researcher to the seasoned ones. More specifically, the book has been focused on the needs of the postgraduate medical student who has to execute a research project and report it through the thesis.
This book provides a comprehensive yet concise presentation of how the research has to be planned, developed, executed, analyzed and reported upon. It has some very good hints on proforma designing, interviewing techniques, protocol writing, statistical analysis, etc. among many others. I believe this book if utilized properly would help in improving the quality of work of the student researcher as well as simplify it and make it enjoyable too.
Prof AK Sood md dnb phd mba mnams
Executive Director
National Board of Examinations
Ministry of Health and Family Welfare
Government of India
FM15Introduction
Welcome to the world of biomedical research. The word research means ‘to search again’ or ‘to examine carefully’. More specifically it means ‘diligent, systematic inquiry or study to validate and refine existing knowledge and develop new knowledge’. The ultimate goal of research is the development of a body of knowledge for a profession or discipline, including those of medicine or dentistry.
Entering a new world requires learning new languages, imbibing new rules and using the newly acquired experiences to interact effectively within that world. As we become a part of this new world, our perceptions and methods of reasoning are likely to be modified as well as expanded. Since research is a new world to most postgraduate biomedical students, we have developed this handbook to facilitate their entry into this world of research.
Research is essential to develop and refine knowledge that can then be used to improve clinical practice. The medical profession is also accountable to society for providing high quality care to patients and their families. The care provided by doctors must, therefore, be constantly evaluated and improved based on new information. Doctors need scientific knowledge to improve their decision-making regarding what care to provide for patients and how to implement that care. A solid research base is also needed to document the effectiveness of selected medical interventions in treating particular patient problems and promoting positive patient outcomes for the greatest numbers of people. Through biomedical research, scientific knowledge can be developed to improve not only medical care and patient outcome but also the health care delivery system at large. Even practicing doctors need to be able to read research reports in order to be able to identify newer and effective interventions for practice, thereby achieving better outcomes for patients and their families.
Yet unfortunately, research has never been a priority in medical academics. In fact, the lack of understanding of research methodology FM16and the paucity of trained researchers has significantly hindered the conduction of medical research, even though research should have been the cornerstone for improving the health of populations.
Participation in medical research can occur at various levels of the medical curriculum; viz. (i) Doctors pursuing the master's degree have to plan and implement a research project and produce a thesis as dissertation (this is supposed to lay the foundation for more formal higher medical research conducted in centers of excellence), (ii) Formal medical research conducted by researchers and faculty of reputed institutes like AIIMS, ICMR, postgraduate medical/dental institutes and many other field level organizations, including the so called Action/Operations Research, (iii) Doctors at other levels also, are often associated with medical research; some of them assist in the conduction of research studies, while, the majority of them are consumers of the research and use research findings to improve their clinical practice.
When we think of research, few words come to our mind like, logical, analytic, systematic, formal, factual, etc. Neurologists and psychologists now associate these words with the functioning of the left side of the brain. The primary functions of the right side of the brain, on the other hand are, seeing relationships, synthesizing them and providing an overview. The words that come to our mind when speaking of this aspect of brain functioning are intuitive, spontaneous, informal, holistic, random, etc. In other words it deals with the creative side.
Research is an effort to understand the world around us, which no doubt is two sided. Therefore, trying to use only one-sided skills and thought processes to understand the world around us, through research can have only limited, if not disastrous outcomes. Research should, therefore, be seen as a process equally reliant on both the creative right as well as the strategic and logical left sided functions of the brain.
Broadly, speaking research can be of two types, quantitative or qualitative. The majority of studies conducted in the field of medicine (including all subfields like dental sciences, nursing sciences, etc.) up to about 1980s used quantitative research methods. Quantitative research is a formal, objective systematic process in which numerical data is used to obtain information about the world around us. This research method is used to describe variables, examine relationship among variables and determine the cause and effect interactions between variables. No doubt quantitative research is still the Sine Qua Non (SQN) of medical research and is the main focus of this book.
Qualitative research on the other hand is a systematic, subjective approach used to describe life experiences and give them a meaning. Though, this type of research is not a new idea in the field of social/FM17behavioral sciences, medical researchers started showing interest in this method only since late 1980s. We have also touched upon this emerging field in brief.
Biomedical Research Methodology deals with the basic concepts and principles of scientific research methods to be used in the field of medicine and health. The book has been developed as an aid for the planning and conduction of medical research. It is intended to be of help right from the formulation of the research problem, setting research objectives, designing the research study, including method of data collection, statistical analysis, up to the stage of interpretation and dissemination of the results.
This book has been specifically designed to provide overall guidance to young researchers like postgraduate students in medical/dental sciences for the conduction of scientific research. It would be especially helpful for the planning and execution of the thesis project which is an essential requirement for the master's degree. It is also intended to be of help to consumers of medical research, whom it will empower to (i) Read the research reports, (ii) Critique these reports and (iii) Summarize the finding of the reports for adopting to their clinical practice. The above three requires an understanding of the research process which has been detailed throughout this book.
Section I deals with the Planning and Execution of Research. It has five chapters; beginning with Planning Your Research. In this chapter, we have dealt with the various stages of a research study and outlined how one can plan his/her research study. It includes details on how to do a review of the literature in the academic library with the help of catalogue, index and the Index Medicus; and also how to search computerized databases through biomedical search engines like medline, pubmed, etc. Planning of the research also needs a thorough knowledge of research designs, sampling, statistical analysis plans, etc. These have been detailed in the subsequent chapter. Planning of the research terminates with writing and finalization of the protocol. Details of how to write the protocol, therefore, forms the tail piece of the research plan.
Chapter 2 deals with the various types of Research Study Designs used for biomedical research. It deals with the routinely used observational methods falling in the descriptive as well as analytical category, and also the experimental ones. Newer, and now more frequently used study designs, viz. the quasi experimental design, hybrid designs (e.g. nested case-control, case-cohort) and various types of qualitative designs (e.g. case study, observations, in-depth interviews, focus groups) have also been included in the discussion. We have also FM18not missed out on the latest technique being used in research, namely the systematic reviews (or the so-called meta-analysis). Naturally, trying to put in so much has made this chapter a bit lengthy.
We felt that, as the researcher proceeded on the planning of his/her research and acquired knowledge about various study design options available to them, they had to be aware of the various Ethical Issues of Research. This forms the third chapter of this book, wherein we begin by introducing the reader to the guiding principles of medical ethics. Then we move on to the relevant guidelines issued by the Indian Council of Medical Research (ICMR), covering handling of research proposals by the Institutional Ethical Committee. The chapter also deals with issues like consent, compensation for participation in research, confidentiality, enrolment of vulnerable groups, and areas in which research is either prohibited or restricted.
The researcher now has a clearer understanding of his probable research topic and this is the stage when he has to plan what he shall be measuring and how. Simultaneously, he has to develop hypotheses he would be testing through his research. This forms the topic of Chapter 4 entitled Hypothesis Development and Measurements. We have discussed the characteristics of a hypothesis and why we try to ‘nullify’ the null hypothesis to reach the research finding. What all can be measured and how these are going to be measured forms the bulk of the remaining chapter. Newer techniques of measurements viz. person-time incidence or hazard density has also been discussed in the text.
The next step of the research process calls for designing and pre-testing the instrument for data collection, proceeding with the data collection, and finally managing such data. This forms the text of Chapter 5 Collecting Data and its Management. We have discussed the steps for constructing the data collection instrument (questionnaire or interview schedule). Further, since biomedical research still follows the traditional methodology, where, interviews with subjects forms the basis for data collection, we deemed it suitable to include a section on interviewing techniques to help our young researchers. The steps to be taken for appropriate treatment of collected data so as to be finally available in the form of a data-base for analysis, has also been discussed. Software packages currently available for data management and subsequent analysis and their salient features forms the last part of this chapter.
Section II of this book is devoted to Biostatistical Applications in Research; the first chapter of this section (Chapter 6), Sampling Issues in Research, is essential for planning of the research. It deals with the various types of sampling. While, we have dealt with almost all types FM19of probability sampling used for biomedical research, we have also touched in brief the methods used for nonprobability sampling techniques followed in public health research. Cluster sampling technique has also been covered. Since adequate sample size is a must for all research and because, calculation of sample size poses huge problem to the beginner, we have given few model sample sizes for certain specific types of studies, which could be taken up and implemented by researchers in their debut work, though it is desirable that they calculate their specific sample size.
The next step in the research process would be summarizing the observations, and this forms the matter of discussion of Chapter 7, Describing Your Observations. Large number of observations seen in research studies need to be bunched together, and these are represented by summary values representative for the series. Two types of such summary values are commonly used in biomedical research; the averages and the dispersions, and we have covered how these are to be derived for grouped as well as ungrouped data series. Almost all the methods used for depicting dispersions have been discussed in brief, namely, variance, standard deviation, standard error, etc.
After data has been collected and compiled, now the researcher would want to know if there is any excess risk or reduced risk in any particular study group or in relation to any particular exposure. The methods to be utilized for reaching such a conclusion needs proper understanding of Assessment of Risk and forms the content of discussion of Chapter 8. We have included both techniques used for assessing risk, direct as well as indirect. In the direct methods we have included risk ratio (or relative risk), risk difference (or attributable risk); and among the indirect methods we have included the relative odds (or odd's ratio), the rate ratios and rate differences for exposure and disease.
Simultaneously with above, further statistical analysis of the research findings has to be done for ascertaining significance of any observed association. This aspect we have covered in Chapter 9, Analyze Your Observations: Check Statistical Significance. This chapter is unique in a way that it discusses in brief many of the currently used statistical techniques used in biomedical research. Among the parametric tests of statistical significance we have included the normal curve or Z test, student's t test (for paired and nonpaired data sets) and analysis of variance (ANOVA). While, we have included the Wilcoxon-Mann-Whitney test, Wilcoxon Signed Rank test, Kruskal-Wallis test, Chi- square test, McNemar's test, among the nonparametric tests. Significant weight-age has been given to the nonparametric tests owing FM20to the fact that these are needed more frequently in biomedical research. All tests have been explained with the help of appropriate examples from the biomedical field.
There is even another aspect of statistical analysis; that dealing with confidence intervals, correlation and regression. These forms of analysis should be included wherever feasible and it forms the text of Chapter 10 Analyze Your Observations: Estimate Confidence Interval, Correlation and Regression.
The last chapter (Chapter 11) of Section II deals with the methods used for presentation of statistical data. We have elaborated the use of tables, graphs, diagrams as well as maps used for various purposes in this chapter entitled Presenting Your Observations.
Section III deals with Concluding the Research and has three chapters; the first of these (Chapter 12) deals with The Basis for Drawing Conclusions and discusses the various types of statistical association, viz. spurious, indirect and direct or causal association. The chapter further analyzes the various theories and concepts used to infer causation; including the necessary and/or sufficient model and Hill's criteria. We close this chapter by including a brief discussion on internal and external validity of research studies.
The second chapter (Chapter 13) of the last section includes the very crucial discussion on Sources of Error in Studies. The main point of discussion here are the various kinds of systematic errors (i.e. bias) namely, selection bias, information bias, confounding, Hawthorne effect, and post-hoc bias. This chapter also includes a brief account of the options available for minimizing the impact of systematic errors.
The last chapter of this section and the book (Chapter 14) has been dedicated to the most important aspect of research, namely Writing the Thesis/Report. Various steps involved in writing the thesis or the report have been dealt with adequately. The most commonly used method of writing the thesis, the so-called standard framework has been discussed in adequate detail. A section has also been dedicated on how to write the bibliographic references, in the Vancouver style for Journal articles, books, chapters in a book, etc.
All the chapters include a list of the key concepts discussed therein, and also have a summary recapitulating the important points worth remembering. A comprehensive Glossary and set of statistical tables (Appendices) has been provided at the end of the book for ready reference.
We hope that this book would be of significant help in the planning and execution of thesis work required of the postgraduate students in various biomedical specialties. Wishing you happy and effective reading.