Clinical Research Scientific Writing. K. A. Koram NMIMR

Clinical Research Scientific Writing K. A. Koram NMIMR

Clinical Research Branch of medical science that determines the safety and effectiveness of medications, devices, diagnostic products and treatment regimens intended for human use. May be Preventive Therapeutic Diagnostic Palliative

The Research Process Conduct Research Report Findings Identify Issues /Problems 3

Steps in conducting Research 1) Identify the problem 2) Determine the purpose of the research 3) Develop the plan or strategy for the research 4) Search for and collect the needed data 5) Analyze the data 6) Write your report 4

Define Research Problem Single out the problem to be studied. Decide on the general area or subject matter for the enquiry. Formulating a research problem: Understand the problem. Rephrase the problem into a meaningful term from analytical point of view.

Steps in Conducting Research 1. Identify the Issue or Problem What do I want to know? Who are involved? Where? Why? 6

Steps in Conducting Research 2. Determine the Purpose What exactly do I want to do here? What is my statement of purpose? To evaluate? To investigate? To compare? To describe? 7

Review concepts and theories and previous research findings The Literature Review Examine (all) the available literature to get acquainted with the research problem. Includes conceptual and empirical literature. Earlier similar studies must be carefully studied. Good sources of material Library, Internet, Digital databases

What is the Purpose of a Literature Review? To demonstrate your scholarly ability to identify relevant information and to outline existing knowledge. To identify the gap in the research that your study is attempting to address, positioning your work in the context of previous research and creating a research space for your work. To evaluate and synthesise the information in line with the concepts that you have set yourself for the research. To produce a rationale or justification for your study.

Formulate Hypotheses State clearly the hypotheses to be tested. Necessary to provide a focal point for the research Specific and related to research question Brings into focus the important parts of the problem

Steps in Conducting Research 3. Draw a Plan or a Strategy Who, where and what are going to be involved in the research? How do I collect the data? What are the deadlines? 11

Steps in Conducting Research 4. Search and Collect the Data Do I need primary data? Do I need secondary data? What are the instruments to be used to collect the data? 12

Steps in Conducting Research 5. Analyze Data How do I process, record, analyze and interpret the data? How do I make connections among the data? How do I draw conclusions from the data? 13

Data Management & Analysis Involves coding, tabulating and drawing out statistical inferences. Condense data into manageable groups Use tables figures and charts to explain the results Use of computers, statistical softwares Use appropriate statistical tests

Analyze, Interpret and Report Analyze data to test the hypothesis (accept or refute) Explain the findings based on some theory Prepare a report on what has been done

Steps in Conducting Research 6. Write the research report What are the major findings of the study? What are the implications? What further questions need be answered?

Steps in Research Process Interpret & Report Analyze data Collect data Design research Formulate hypotheses Review concepts and theories Review previous research findings Define research problem

How do you translate your research ideas into a blueprint? By defining the specific aims of the study Write out the specific aims of your study Design the study such that it will answer the specific questions you are asking

Research Plan (Protocol /Proposal) Blueprint for what will be done in the research Importance Sets boundaries and prevents blind search Collect data with the maximum efficiency Least cost, minimal effort, time, Reliability of results Firm foundation for the research process No misleading conclusions Helps to organize ideas

The Research Plan (Protocol /Proposal) Define precisely Aims and objectives Nature of measurements to be made Population to be studied To produce a document that gives clear ideas of the aims and objectives of the study to all concerned

The Research Plan (Protocol /Proposal) What is the study about? Why the study? Significance of the study Scope Objectives Hypothesis to be tested Major concepts to be defined Criteria for measurements Place, time and duration of study Design (study type) Sample design, size, sampling strategy Data types, sources, collection methods, tools, processing & analysis methods Target audience

Data collection Several ways for collecting data, e.g. Observation Personal interviews Questionnaire Lab measurements

There are different kinds of study designs Experimental studies Clinical trials (gold std) Community trials Therapeutic/preventive trials Single/multi-site trials Observational Studies Cohort studies Case-control studies Nested case-control studies Cross-sectional studies Ecological studies

Classification of Study Designs Epidemiological Studies Non Experimental (Observational) Experimental (Interventional) Group Data Individual Data Group Data Individual Descriptive Analytic Descriptive Analytic Community Trial Clinical Trial Ecologic al Study Cross Sectional Study Cohort Study Case Control Study

Hierarchy of Evidence Randomized Double Blinded Control Trials Cohort Studies Systematic Reviews and Meta Analysis Case Control Studies Case Series Ecological Studies; Cross Sectional Studies Case Reports Ideas, Editorials, Opinions Animal Studies In vitro (test tube) research

Clinical Trials Clinical trials are used to evaluate the safety and efficacy of a new product; a new formulation or combination of existing product(s); or a new clinical indication for an existing approved product There are many ethical issues to consider when conducting clinical trials, as they involve experimentation on human beings

Intervention Trials General Structure Researcher selects and randomly assigns individuals (or groups) to treatment or non-treatment groups. Select participants by defining specific exclusion/inclusion criteria. Perform sample size/power calculations to define the number of subjects to be selected. Participants are followed forward in time. Incidence of outcome (ie., disease, survival, death) are compared between groups.

Basic Trial Design Population PRESENT Sample Ra n d o m i s a t i o n Intervention 1 New Treatment Intervention 2 (placebo) /Current Treatment FUTURE Not Improved Improved Not Improved Improved Steps: 1. Select sample from reference population 2. Measure the outcome variables before intervention 3. Randomize the participants 4. Apply the product to be compared 5. Follow-up for therapeutic or prophylatic effect 6. Measure surrogate variables of potential effect Adapted from Hulley & Cummings, 1988 & Leon Gordis, 2000

RCT Design Controlled Clinical Trials Gold Standard (for providing (epidemiological) evidence for causation Not always possible /best to perform RCT Unnecessary Inappropriate Impossible inadequate

Case Report /Series Reviews a series of charts of patients Summarizes the information Journal article

Descriptive Study Analysis Describes person, place or time using: Tables: frequency distributions Rates Graphics: charts and Maps

Cross-sectional studies General Structure Snapshot of the population Useful for describing variables and their distribution patterns. e.g., Ghana Demographic and Health Survey (GDHS) a major source of information about the health and habits of the Ghanaian population. Collected every 3 to 5 years but is a snapshot of the health and habits of the people.

Cohort Studies General Structure Start with exposed vs. unexposed Similar to intervention trials except patients are not randomized to groups. Need to have a good idea of which exposures are suspected as possible causes of disease. Retrospective or prospective

Cohort Studies General Structure [3] Defined Population Non-randomized Exposed Non-exposed Disease No Disease Disease No Disease

Case Control Studies

Case-control studies General Structure Start with diseased (case) vs. non-diseased (control). Examine the relationship of exposure status to disease status. Efficient when outcome is rare. Match controls to cases based on major factors related to the disease but not of interest to the investigator. The number of controls per case can be different than 1:1.

Sampling Strategy Points to look out for Sampling unit Who is to be surveyed? Sample Size How many people should be surveyed? Sampling Procedure How should the respondents be chosen?

Types of Samples Probability sample Simple random sample Stratified random sample Cluster sample Non Probability sample Convenience sample Judgement sample Quota sample /systematic sample

Probability sample Simple random sample Every member of the population has a known and equal chance of selection. Stratified random sample The population is divided into mutually exclusive groups (such as age groups), and random samples are drawn from each group Cluster sample The population is divided into mutually exclusive groups (such as blocks), and the researcher draws a sample of the groups to interview

Non Probability sample Convenience sample The researcher selects the easiest population members from which to obtain information. Judgement sample The researcher uses his or her judgement to select population members who are good prospects for accurate information. Quota sample (systematic sample) The researcher finds and interviews a prescribed number of people in each of several categories.

Issues to Consider in Errors of estimation /measurement Use good study design Researcher User large numbers and a well drawn sample Estimate or Measure = True Value + Bias + Random Error Critically Appraise Desing Reader /consumer of research Confidence Intervals and P- values

Conclusion The beginning of good study design is a good plan define your specific aims writing them out in no more than 1-2 sentences per aim. The choice of intervention or observational trials will be guided by the questions your specific aims raise. Intervention trials good for determining causality; however, randomization not always ethical. A variety of observational trials are available. The best choice is determined by your outcome of interest and what, if any, time frame that is of interest.