PHAR 628 Research Methods & Biostatistics Lecture 2 PDF

PHAR 628 Research Methods & Biostatistics Lecture 2: Research Design Lixian Zhong, Ph.D. Jan 17th, 2025 PHAR628 LECTURE 2 1 PHAR628 LECTURE 2 2  Obje...

PHAR 628 Research Methods & Biostatistics Lecture 2: Research Design Lixian Zhong, Ph.D. Jan 17th, 2025 PHAR628 LECTURE 2 1 PHAR628 LECTURE 2 2  Objectives ❖To understand research design terminology ❖To describe classification of research designs in clinical research ❖To explain importance of validity in research design PHAR628 LECTURE 2 3  Introduction ▪ Research design constitutes the critical backbone for a sound scientific investigation. A good design increases the validity of research findings A flawed design could raise questions on the credibility of those findings ▪ Poorly designed studies have limited scientific value and when incorporated into evidence-based practice could be useless, wasteful, or sometimes harmful to patients. ▪ An understanding of research designs is essential to evaluate and apply research evidence. PHAR628 LECTURE 2 4  Research Design ▪ Research design refers to the overall plan that allows researchers to gather answers to study questions and test study hypotheses. ▪ The decision to use a particular study design hinges on the ability of that design to provide valid results. ▪ At its core, validity reflects the accuracy of study results. PHAR628 LECTURE 2 5  A thinking exercise A pharmaceutical company developed a new diabetes drug candidate X1327. They recruited 1,000 patients with type 2 diabetes between 18-65 years old and without severe comorbidities in the clinical trial. All patients received the investigational new drug, which was taken orally twice a day. At the same time, all patients received a training on healthy lifestyle for diabetes management, including healthy eating and regular exercise. At baseline the average HbA1c was 8.8 and after three months, the average HbA1c was 7.2, and it was statistically significant from baseline value. The drug was generally well tolerated, and no severe adverse events were observed. The company claims that the diabetes drug is effective in reducing HbA1c in type 2 diabetes patients. Does this study provide good validity? PHAR628 LECTURE 2 6  Research Design Validity can be further distinguished into internal validity and external validity. ◦ Internal validity reflects the extent to which clinical outcome of interest (dependent variable) in a study is caused by the treatment (independent variable). ◦ External validity refers to the extent to which the results of a study can be generalized to other settings. PHAR628 LECTURE 2 7  Research Design Classification Research designs can be classified using different sets of criteria, which includes study purpose, time orientation, experimental setting etc. Although these classifications capture different dimensions of research approaches, these classifications are interlinked and sometimes can overlap. PHAR628 LECTURE 2 8  Research Design Classification Research Design Time Experimental Study Purpose Orientation Setting 1 Descriptive Analytical Prospective Retrospective Experimental Observational PHAR628 LECTURE 2 9  Research Design Classification - Purpose ◦ The purpose of the study could be either descriptive or analytical. ◦ A researcher may decide on a particular design to just describe a phenomenon (descriptive) or provide interpretation of relationship and/or causal mechanism that may exist between two or more variables an existing phenomenon (analytical). PHAR628 LECTURE 2 10  Research Design Classification - Purpose ◦ Descriptive studies, as the name implies, describe or summarize information about the disease or events without making any causal inferences. ◦ Descriptive studies incorporate five important elements pertaining a new disease or event - Who - What - Why (proposed possibility, not proven) - When - Where PHAR628 LECTURE 2 11 PHAR628 LECTURE 2 12 PHAR628 LECTURE 2 13 Research Design Classification - Purpose ◦ Analytical studies are aimed at understanding the relationship and/or causal mechanism that may exist between two or more variables. Correlation does not imply causation! http://changetheratio.tumblr.com/post/2701038755/correlation- doesnt-imply-causation-but-it-does PHAR628 LECTURE 2 15  Causation Causation is one of the most commonly used terms in the scientific literature. Cause-and-effect relationship or causality exists if there is a causal relationship between the treatment (cause) and clinical outcome (effect). Establishing cause-and-effect relationships can help develop rational solutions to clinical problems. PHAR628 LECTURE 2 16  Causation ▪In 1965, Sir Austin Bradford Hill listed a set of nine criteria that should be fulfilled for relationship between two variables to be considered as potentially causal – “Bradford Hill” criteria. ▪As acknowledged by Hill, the fulfillment of the nine criteria does not automatically imply causation, but rather assist researchers in making decisions regarding the presence or absence of causal mechanisms. PHAR628 LECTURE 2 17 PHAR628 LECTURE 2 18  Research Design Classification Research Design Time Experimental Study Purpose Orientation Setting 1 Descriptive Analytical Prospective Retrospective Experimental Observational PHAR628 LECTURE 2 19 Research Design Classification – Time Orientation ◦ Research designs may be classified as prospective or retrospective. Retrospective Prospective Exposure Outcome Exposure Outcome Past Present Future PHAR628 LECTURE 2 20 Research Design Classification – Time Orientation Retrospective studies involve evaluation of data of past events or existing data such as medical records to achieve the research objective. In retrospective research, the event of interest has already occurred, and researchers go backwards in time to determine the relationship between cause and event. ◦ The main advantage of retrospective design is that they are minimally resource intensive as it only involves analysis of existing data or past events. ◦ Limitations: the researcher cannot control past events or data collection methods. Consequently, they have to rely on existing data or previous events without any say on what variables are needed and how they are defined and collected. PHAR628 LECTURE 2 21 Research Design Classification – Time Orientation Prospective studies are those where the researcher collects the data after the study onset by following individuals over a period of time. ◦ The main strength of this design is to determine and define the research variables and prospectively collect relevant data to achieve the objectives. ◦ The main limitation of prospective design is that they are resource (time and cost) intensive. PHAR628 LECTURE 2 22  Research Design Classification Research Design Time Experimental Study Purpose Orientation Setting 1 Descriptive Analytical Prospective Retrospective Experimental Observational PHAR628 LECTURE 2 23 Types of Research Designs – Experimental Setting ▪ Research designs can be broadly categorized into two types: observational and experimental designs. ▪ In observational designs, the researcher merely observes the interplay of independent variable (exposure or treatment) with the dependent variable (outcome). ▪ In experimental designs, the researcher controls the independent variable (exposure or treatment)to see if it will have an impact on the dependent variable (outcome). Also referred to as “interventional studies”. PHAR628 LECTURE 2 24  Experimental Designs ◦ In experimental designs, the researcher controls the treatment (independent variable) that is likely to have an impact on clinical outcome (dependent variable). ◦ There are three essential elements of a true experiment. 1) The independent variable (treatment) must be manipulated by the researcher 2) The study subjects are randomized into groups 3) A control or comparison group must be incorporated within the design ◦ Other criteria such as temporality, strength, biological gradient, etc. can easily be achieved in experimental studies to draw causal conclusion. ◦ Basic researchers often rely on experimental designs to test their research hypothesis. PHAR628 LECTURE 2 25  Experimental Designs ◦ The most commonly used experimental design in clinical research is the Randomized Controlled Trial (RCT). ◦ Also referred to as Randomized Clinical Trials. ◦ The RCT is considered to be the gold standard in evaluating the safety and efficacy of an intervention. ◦ RCTs in general have high internal validity. ◦ Since RCTs are conducted in tightly controlled clinical settings, RCTs tend to have low external validity (generalizability). PHAR628 LECTURE 2 26 Questions: 1. Randomized clinical trials follow a ____________ research design. A. prospective B. retrospective 2. Randomized clinical trials are ___________ studies. A. descriptive B. analytical PHAR628 LECTURE 2 27  Observational Designs ◦ In observational studies, as the name suggests, a researcher observes the relationship between the study variables, mainly independent (exposure or treatment) and dependent (outcome or disease) in a natural setting. ◦ Unlike experimental studies, there is no manipulations of the independent variable or randomization of participants into experimental and control group. ◦ The variations in exposure and outcomes are observed to evaluate their relationship or association. PHAR628 LECTURE 2 28  Observational Designs ◦ In observational studies, investigators collects data regarding exposure and outcomes using primary data techniques like interviews, surveys, etc., or use data collected previously for other purposes (secondary data) like medical charts. ◦ Observational studies include the following: case reports, case series, cross-sectional studies, case-control studies, and cohort studies. PHAR628 LECTURE 2 29  Observational Designs A case report involves a study of a single case of a new disease or manifestation, while a case series involves a study of multiple similar cases. PHAR628 LECTURE 2 30  Observational Designs Cross-sectional studies are those wherein the exposure and/or outcome of interest are measured at the same point in time. They can be purely descriptive, such as prevalence studies or are used to ascertain the relationship between variables of interest, such as through analytical cross-sectional surveys. PHAR628 LECTURE 2 31  Observational Designs Case-control studies involve comparison of exposure status among individuals with the disease or outcome of interest (cases) and those without (controls). PHAR628 LECTURE 2 32  Observational Designs Cohort studies are observational studies wherein two groups, i.e., exposed and unexposed, are followed over a period of time until the development of outcome of interest. Cohort studies can be divided into two types: prospective and retrospective. ◦ In prospective cohort study, the exposed and unexposed groups are classified at baseline and then followed in future to determine the occurrence of outcome of interest in the two groups. ◦ In retrospective cohort study, a researcher uses previously collected (historical) data to identify exposure status and occurrence of outcome in the study group. PHAR628 LECTURE 2 33  Research Design Summary Research design descriptive analytical Observational Observational Experimental studies studies studies Case cross-sectional Case-control Cross-sectional Cohort studies RCTs reports/series studies studies studies Retrospective studies Prospective studies Prospective Retrospective cohort studies cohort studies PHAR628 LECTURE 2 34