International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491
Vol 5, Issue 3, 2013
OVERVIEW OF STUDY DESIGNS Dr. SRIKANTH*1, Dr. PRAVEEN KUMAR DODDAMANI 2 1Department
of Pharmacology, Khaja Banda Nawaz institute of medical sciences, Gulbarga, 585104, India, 2Department of Microbiology, Mediciti institute of medical science, Ghanpur village, Medchal Mandal, R.R district, Andhra Pradesh, 501401, India. Email: [email protected]
Received: 23 Apr 2013, Revised and Accepted: 29 May 2013
ABSTRACT Study design is the procedure under which a study is carried out. “The rules that govern the process of collecting and arranging the data for analysis are called research designs”. Study designs could be either descriptive or analytical. In observational study design, the researcher observes and does not intervene, whereas in analytical study, some kind of intervention is done. Descriptive observational study designs are useful for only generating hypothesis, whereas analytical observational study designs are helpful for both generating and testing hypothesis. Each type of study design represents a different way of collecting information. Each has its own advantages and disadvantages. Depending on various factors such as the type of research question, time available for study, resources available for the study, quality of data from various sources, earlier studies, feasibility, statistical and regulatory issues, the investigator has to choose the appropriate study design which will answer his particular research question. This article gives a brief overview of the various study designs commonly used in research except experimental designs. Keywords: Study design, Descriptive, Analytical, Case-control, Cohort
Study design is the procedure under which a study is carried out. Each type of study design simply represents a different way of obtaining information. In other words “The rules that govern the process of collecting and arranging the data for analysis are called research designs”.
Epidemiology is the study of the distribution and determinants of disease frequency in human populations and the application of this study to control health problems [1, 2]. The term study includes both surveillance, whose purpose is to monitor aspects of disease occurrence and spread that are pertinent to effective control  and epidemiologic research, whose goal is to harvest valid and precise information about the causes, preventions, and treatments for disease.
Overall, the study design tree can be divided into two broad categories of descriptive and analytical studies . An overview of these study designs is shown in Figure 1.
Case series, case reports
Case control Cross sectional Ecological
Fig. 1: Basic study designs . RCT = Randomized control trials Some investigators also include integrative studies as a type of study design which includes Meta-Analysis. Decision Analysis, cost effective analysis. Evidence-based medicine classifies different types of studies on the basis of research design as the criterion for hierarchical
rankings . Randomized control trials (RCTs), systematic reviews and meta-analysis of RCTs are at the top of the pyramid, while anecdotal evidence is at the bottom  as shown in Figure 2. However, the evidence pyramid does not provide the disclaimers that all study designs are not possible to conduct to answer all research questions.
Srikanth et al. Int J Pharm Pharm Sci, Vol 5, Issue 3, 1020-1024
Systematic reviews, Meta analysis RCTs Cohort Case control Case series Case reports Expert opinion, editorials Animal research In vitro research
Fig. 2: Hierchary of evidence pyramid .
Another way of classifying the hierarchy of strength of evidence for treatment decisions is based on level of evidence . Levels of Evidence
Descriptive studies examine differences in disease rates among populations in relation to age, sex, race, and differences in temporal or environmental conditions. Descriptive study designs are helpful in generating a hypothesis .
Level I: N of 1 randomized trial (double-blinded, cross-over)
Level I (A): Systematic reviews of randomized trials
Seek to measure the frequency in which diseases occur or collect descriptive data on possible causal factors
Describe occurrence of outcome
Used to organize and summarize data according to time, place, and person.
Level I (B): Single randomized trial Level II (A): Systematic review of observational studies addressing patient-important outcome Level II (B): Single observational study addressing important outcome
Describe natural history of disease
Level III: Physiologic studies
Extent of public health problem
Level IV: Unsystematic clinical observations (case-reports, anecdotal)
Identify populations at greatest risk
Allocation of health care resources
Suggest hypothesis about causation
Often used for generating hypotheses for further research.
Choosing an established design gives you a huge head start in design, analysis and eliminating bias. Choice of a study design to depends on: •
What is the research question
Time available for study
Resources available for the study
Common or rare disease
Type of outcome of interest
Quality of data from various sources
Medical, statistical and regulatory issues
These studies deal with presentation of a single case or handful of cases in detail. They are most likely to be useful when the disease is uncommon.
Earlier studies, feasibility
Generally report a new or an unique finding
Descriptive epidemiology This is the first foray into research. These studies describe the frequency, natural history and determinants of a factor or disease. It is a study to identify patterns or trends in a situation, but not the cause and effect linkages among its different elements.
Generally speaking, these studies can only identify patterns or trends in disease occurrence over a period of time or in different geographical locations but cannot ascertain the causal agent or degree of exposure. Case Reports
e.g. previous undescribed disease
e.g. unexpected link between diseases
e.g. unexpected new therapeutic effect
e.g. adverse events
Srikanth et al. Int J Pharm Pharm Sci, Vol 5, Issue 3, 1020-1024 Example of a case report Initial report of five cases of pneumocystis pneumonia in previously healthy, homosexual men. MMWR 1981; 30:250-2. Case Series A case series is a descriptive study that occurs in a group of patients who have a similar diagnosis or who are undergoing the same treatment over a certain period of time. Generally report on new or a unique condition. An outline of case report/series is shown in Figure 3.
Analytical studies are classified into two main categories of observational and experimental designs. In experimental studies, researchers make a decision on the assignment of exposure or intervention, while in observational studies exposure is not assigned by the researcher . In observational studies, a specific population is observed versus assigned and the information is collected on outcomes according to exposure. That is, unlike experimental study designs, the investigator does not control the assignment of exposure and is only involved passively in collecting data on exposure followed by outcomes assessments. Cross-sectional studies
Fig. 3: Outline of a case report/series . Advantages of a case report/series •
Provides first sign to identify a new disease or adverse effect
Useful for hypothesis generation
Characterizes averages for disorder
Provides information for very rare disease with few established risk factors
A cross-sectional study “examines the relationship between diseases (or other health-related characteristics) and other variables of interest as they exist in a defined population at one particular time”. Cross-Sectional Studies measure existing disease and current exposure levels. They provide some indication of the relationship between the disease and exposure or non-exposure. Cross-sectional studies are fairly common in occupational settings using data from pre employment physical examinations and company health insurance plans . A diagrammatic representation is depicted in Figure 4. Examples of Cross-sectional studies 1) Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA 2004;291:2847-50. 2) Prevalence of renovascular disease in the elderly. J Vasc Surg 2002;36:443-451.
Cannot study the relationship between cause and effect
Cannot assess disease frequency
Minor relevance to public health
Usually small sample size
Example of a case series Creech JL, Jr, Johnson MN. Angiosarcoma of liver in the manufacture of polyvinyl chloride. J Occup Med. 1974 Mar;16(3):150–151 Community survey (Surveillance or descriptive cross sectional study) Descriptive cross-sectional (survey based) are conducted to estimate the frequency and distribution of a disease. In this study, information is collected on several individuals at one point in time about their health status, behavior, or other risk factors. Surveillance can be either active or passive. Passive surveillance relies on data generally gathered through traditional channels, such as death certificates. By contrast, active surveillance searches for cases. Epidemiological surveillance has made important contributions to health, but none more impressive than smallpox eradication. Surveillance and containment were responsible for the elimination of smallpox from the world, an extraordinary public-health achievement . Analytic epidemiology These studies attempt to specify in more detail the causes of a particular disease. They
Fig. 4: Outline of cross sectional study . Advantages •
Good design for hypothesis generation
Estimation overall and specific disease prevalence can be done
Can estimate exposure proportions in the population
Good design to study multiple exposures or multiple outcomes or diseases
Easy, quick and inexpensive
No ethical issues
Usually used as first step for new study issue.
Not a useful for establishing causal relationships
Hard to decide when disease was actually acquired
Weakest observational design, (it measures prevalence, not incidence of disease).
The temporal sequence of exposure and effect may be difficult or impossible to determine
describe association between exposure and outcome and causation
Rare and Quickly emerging diseases a problem, Confounding is difficult to control
Provides a control group (baseline)
Test hypotheses about determinants
Susceptible to selection bias (e.g. selective survival) and misclassification (e.g. recall)
Srikanth et al. Int J Pharm Pharm Sci, Vol 5, Issue 3, 1020-1024 Case-control studies Case–control study is a method of sampling a population in which researchers identify and enroll cases of disease and a sample of the source population that gave rise to the cases. Case-Control Studies identify existing disease/s and look back in previous years to identify previous exposures to causal factors . •
Cases are those who have a disease.
Controls are those without a disease.
In a retrospective case-control study, the assessment of the exposure or risk factor occurs after subjects are classified as cases or controls. In a prospective case-control study, all measurements of the exposure or risk factor variables are recorded before subjects are classified as cases or controls. A diagrammatic representation of a case control study is shown in Figure 5.
time or till the disease occurs. When the study commences, the outcomes have not yet developed and the investigator must wait for them to occur. In a retrospective cohort study, both the exposures and outcomes have already occurred when the study begins. Because high rates of follow-up are critical to the success of a cohort study, investigators have developed many methods to maximize retention and trace study participants . For prospective cohort studies, strategies include collection of information (such as name and date of birth) that helps locate participants as the study progresses. In addition, regular contact is recommended for participants in prospective studies. These contacts might involve requests for up-to-date outcome information or newsletters describing the study’s progress and findings . A schematic diagram of prospective cohort study and retrospective cohort study is shown in Figure 6 and 7 respectively.
Examples: 1) Case-control studies of aspirin and Reye's syndrome 2) Herbst AL, Ulfelder H, Poskaner DC. Adenocarcinoma of the vagina: Association of maternal stilbesterol therapy with tumor appearance in young women. N Engl J Med 1974;284:878-881.
Fig. 6: Prospective Cohort study . Examples of prospective cohort study: 1) Framingham Heart Study 2) Doll R, Hill AB. The mortality of doctors in relation to their smoking habits: A preliminary report. Br Med J 1954;228:14511455.
Fig. 5: Case control study . Advantages •
Best design for rare diseases
Can be completed quickly since events of interest have already occurred
Various potential exposures can be studied at the same time
Best suited for hospital-based studies and outbreaks
Less expensive and time consuming
Small sample size
If assumptions are met, valid estimates of relative risk
Fig. 7: Retrospective Cohort study . Examples of retrospective cohort study: 1) Predictors of hospitalization and death among pre-dialysis patients. Nephrol Dial Transplant (2000) 15:650-658
Problems with temporal sequence of data
May miss diseases which are in latent period
Can’t calculate attributable risk
Can only study one outcome and have a high potential to bias
Disease status can influence selection of subjects
2) Liddell FDK. The development of cohort studies in epidemiology: a review. J Clin Epidemiol 1988; 41(12):1217-1237. relative
Advantages of Cohort Studies •
Can be the best assessment of exposure and study of rare exposures
One of the best design if exposure needs to be measured directly
Only way to get prospective information for fatal diseases
A cohort is defined as a group of people with a common characteristic or experience.
Describes the natural history of disease
In a prospective cohort study, subjects are grouped on the basis of past or current exposure and are followed up for a fixed period of
Can examine multiple outcomes linked to exposure
Can estimate both overall and specific disease rates
Srikanth et al. Int J Pharm Pharm Sci, Vol 5, Issue 3, 1020-1024 •
No recall and selection bias, more conclusive results than casecontrol studies
Disadvantages of Cohort Studies •
Impractical for rare diseases
May not be statistically significant
Larger sample size than case-control, very expensive
Long time commitment for follow-up
Ecologic Studies (Co relational studies) A classical ecologic study examines the rates of disease in relation to a factor described on a population level. Thus, “the units of analysis are populations or groups of people rather than individuals”. Ecologic studies that identify groups by time often compare disease rates over time in geographically defined populations. For example, investigators conducted an ecologic study to compare HIV seroprevalence changes over time among injecting drug users in cities with and without needle-exchange programs . The geographical information system (GIS) is a very useful new tool that improves the ability of ecologic studies to be able to determine a link between health data and a source of environmental exposure.
2. 3. 4.
For example, if we study the frequency of a characteristic (e.g. cigarette smoking) and some outcome of interest (e.g. lung cancer) occurring in the same geographic location (e.g. a city, state or a country). These studies can be used for generating hypotheses but not to draw causal conclusions because we do not have information as to whether people who smoke cigarettes are the same people who developed lung cancer. Advantages include low cost, wide range of exposure levels, and the ability to examine contextual effects on health. Limitation is lack of information on important variables.
In this paper, we primarily focus on the descriptive and analytical studies excluding experimental designs. Epidemiologists use both experimental and observational study designs to answer research questions. While RCTs provide most accurate answers to questions related to efficacy of competing interventions, they are not suited to answer research questions related to prognosis or diagnostic accuracy issues. Therefore, investigators are encouraged to choose a appropriate study design to match the research question. For this a thorough understanding of the research question is necessary in order to select the best study design. Choosing an appropriate study design to address a research question is the first important and a very critical step to obtain valid results. For hypothesis generation, observational, descriptive studies are generally used whereas for generation as well as hypothesis testing, analytic studies like case-control, cohort studies are commonly employed.
10. 11. 12.
16. 17. 18. 19. 20.
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