This action might not be possible to undo. Are you sure you want to continue?
Dr. Nashwa Radwan Professor of Public Health and Preventive Medicine
بسم ال الرحمن الرحيم
To understand the concepts of different study designs To learn about the advantages and disadvantages of several study design. To be able to choose the best study design to assess certain health problem.
What is research?
Research is the manner by which we attempt to solve problems or to conform the validity of the solutions to problems
The basic aim of clinical research is to advance knowledge of human health and illness . 1-Assess the health status or clinical characteristics of a well defined population the annual rate of suicide in teenager . The incidence of rabies in certain locality. 2-Probe the natural history of the disease … The clinical course of retinopathy in diabetics over 10 years follow up.
Examine clinical decision- making processes … The best screening test for glaucoma in general population. 4-Determine and assess treatment outcomes . … Tumor response of laryngeal cancer in patients who receive radiation . 5-Identify and assess risk factors The incidence of lung cancer in smokers relative to non smokers
Principles used in :assessing such data
Efficacy: describes the true treatment or intervention effect under ideal condition Effectiveness :describes the true treatment or intervention effect under routine condition . Reliability : describes the reproducibility of the test results . Bias : is a systematic error that is unintentionally made . Sensitivity :describes test positives or true abnormal correctly identified . Specificity : describes test negatives or true normal correctly identified .
What the types of epidemiological studies?
Use an existing phenomena in attempt to understand aspects of health or illness . The investigator neither control the population nor the factors to which the population is exposed . a-Case report study. b-Case series study. a-Cross sectional or prevalence study. b-Retrospective or casecontrol study. c-Prospective or incidence study.
Test the effect of some intervention on a certain aspect of health or illness . The investigator can control both the population and the factors to which the population exposed . a-Single blind. b-Double blind. c-Trible blind.
Types of Epidemiologic Observational Studies
based on: type of sampling from population based on Exposure &/or Disease or neither temporal sequence of observation one time point, forward, backwards
Types of Studies
A. Experimental - study factor is manipulated by the investigator Types
1. Pure versus Quasi-experimental 2. Laboratory versus real world
B. Observational - no manipulation of study factor by the investigator
1. Descriptive versus Analytic 2. Retrospective versus Prospective
Is a brief objective report of clinical characteristic or outcome from a single clinical subject or event -Study question : It is commonly used to report unusual or unexpected events -Examples: A report of advanced diabetic retinopathy in a patient with no other clinical evidence of diabetes .
A single event first must be identified . Data collection generally is retrospective ,with a review and a descriptive summary of subject or event . No statistical analysis or comparative group is included -Strengths and limitation : It provides the first report of unexpected event, hypotheses for testing and definition of issue for further study. But the results are rarely generalized
B-Case series report:
An objective report of a clinical characteristics or outcome from a group of clinical subjects . -Study question : Report new diseases or health related problems . -Examples : Is one that identified several children with birth defects who were born to mothers who had taken thalidomide.During pregnancy.
-Methodology : Subjects must be identified with regard to the clinical characteristics Data collection may be retrospective or prospective , but a control or comparison group is not included Descriptive statistics are calculated - Strengths and limitations : Generalization of the results is limited because ; the selection of study subjects is unrepresentative and lack of comparison group
Cross-Sectional Study – Prevalence Study
Cross-Sectional Studies measure existing disease and current exposure levels. This study analyzes data collected on a group of subjects at one time rather than over a period of time The method of research that simply looks with intense accuracy at the phenomena of the moment (what is happening? Right now) and then describes precisely what the researcher sees.
The point should be clearly emphasized that looking or seeing is not restricted to perception through the physical eye. In research we have many ways of seeing; examples -The physician looks at the heart through a stethoscope and electrocardiogram. -The educator and the psychologist look at intelligence, attitude, believes through IQ tests, attitude scales and other evaluation scales. -The epidemiologist looks in survey through interview and questionnaire.
sample without knowledge of Exposure or Disease sample at one point in time Mostly prevalence studies/surveys
-Study question: Concern the occurrence of the disease and the rate of other events In a single point of time( the prevalence) -Example: The rate of occurrence (prevalence) of smoking among high school students at a particular point of time. -
The population for the study must be carefully chosen, clearly defined. Target population is surveyed at a single (particular) point of time (e g. one year).. The rate of occurrence of diseases and events among the target population in a particular point of time (e.g.the prevalence) is calculated. No statistical analysis is included.
Strengths and Limitations:
-It is quick, cheap and easy -True rates are determined (the prevalence). - The prevalence rate is used as a measure of health status in the population of interest and for comparisons between different populations and communities. - Can study multiple exposure and multiple diseases.
Impractical for rare diseases Not a useful for establishing causal relationships. It does not allow us to answer the question ,which came first (which caused which) No control over sample size for each exposure by disease subclass. Data are particularly susceptible to distortion through the introduction of bias into the research during sampling questionnaire and interviewing.
How Bias Enters the Research Design
Example: A researcher decides to use a city telephone directory as a source for selecting a random sample.He will open a page at a random, close his eyes, put the point of the pencil down on the page, and the names that comes to the pencil point will be selected.you can not get much more random than that. But the evil spirit of bias is there. HOW?
D- Case – control study – Retrospective Study:
An observational study in which diseased and non- diseased (controls) subjects are identified after the fact and then compared regarding specific characteristics to determine possible association of risk for the disease .
Case-Control Studies identify existing disease/s and look back in previous years to identify previous exposures to causal factors. Analyses examine if exposure levels are different between the groups.
Cases are those who have a disease. Controls are those without a disease. look back in previous years to identify previous exposures to causal factors.
Study question : Address the issue relating to risk factors for disease by comparing the effect of a particular factor in diseased population to that in non-diseased population . -Examples : Comparing the rate of smoking in normal subjects and patients with lung cancer.
Find cases of the disease and obtain from them or about them the history of the assumed cause exposure. Find control persons similar to the cases, and similarly obtain histories of exposure from them. Statistical analysis is done between both groups to determine that the difference between two groups is real not to chance . Conclusion are useful for generation of hypotheses and for initial evidence of risk association
Strengths and limitation
are easily available (usually hospital based) . Thus, its the method of choice for rare diseases.
-Historical data are often available from clinical records of patients, So it is possible to use these data without obtaining further information from case or controls.
It is quick and cheap as the disease of interest has already occurred.
-It tends to support, but not prove, causal hypotheses by establishing associations of risk factor.
in data collection: - The study is un masked. ( since the presence or absence of disease is known to the subject and the observer). -Recall bias may also occur because exposure to risk factor is often dependant on memory of subjects. -Bias in the selection of subjects : (Non-representative ness of cases) since a case control study is not population – based such fallacy is called( Berkson Fallacy). -The occurrence of the assumed cause is obtained from the history of the selected cases and controls Thus we can not know which occurred first? (Which Caused Which) .
E- Cohort –ProspectiveIncidence Study
It is an observational study in which exposed and non exposed population are identified and followed prospectively over time to determine the rate of a specific disease or event . -Study question : Address issues relating to risk factors by comparing population exposed to a factor under study to population that are not exposed . -Examples: The incidence of lung cancer in smokers to nonsmokers .
Exposed and non exposed population. Follow prospectively over time. Measure the incidence rate.
a-A population of exposed and non exposed must be determined and followed prospectively for a certain period of time(e.g. one year) b- Exposure to risk factor under study. c-The incidence rate of disease or an event for both exposed and non exposed must be calculated and the relative risk is measured . d-Statistical comparison is made between exposed and non exposed to assess that the observed difference is real not due to chance
Strengths and limitation
-Costly and time consuming due to the need for large number of subjects and prolonged time of follow up -Potential bias in recall and selection is lessened -Allows study of rare diseases. -The results is considered more conclusive than casecontrol study -Allows for determination of a population –based rate of new disease or event(e.g.the Incidence Rate) and the Relative Risk .
How do we calculate the Incidence Rates(IR)? How do we calculate the Relative Risk(RR)?
F- Clinical trial :
It is an experimental study used to assess the differences between two or more groups receiving different interventions or treatments .
Study question :
To compare outcomes between different intervention .
A comparisons between chemotherapy to chemotherapy plus radiation for laryngeal carcinoma . Testing different types of vaccines on population of children to prove their efficacy in preventing the diseases. -Testing different forms of health service delivery.
-Types: -Single blind:When the studied persons do not know whether they belong to the treatment or the control group. -Double blind: When this knowledge is not known by both the studied persons and the experimenter. -Triple blind:When this knowledge is not known by all the three parties; the studied persons, the experimenter, and the statistician.
a-A population with a clinical characteristic requiring intervention must be determined . b-Subjects must be allocated , randomly , to each of the treatment intervention . c-Treatments are administrated in an identical or controlled manner . d-Treatment outcomes and other results ( side effect , costs , benefits ) must be measured . e-Statistical analysis is made to compare the rates of measured treatment outcomes .
Strengths and limitations : a-A clinical trial allows for control of all variables ,which can also affect outcomes under investigation . b- An insufficient number of subjects may lead to failure to detect true differences .
-Description: Meta- analysis seeks to combine the results of several clinical studies on the same issue to derive definite conclusion from the varied and sometimes contradictory results. Similar to a review article, a meta- analysis begins with a literature review identifying studies of a similar research question. Unlike a review article, meta- analysis attempts to analyze statistically the aggregate results to drive a single integrated conclusion.
Describe on the best clinical approach to a problem based on several related studies
-Fibrinolytic therapy for acute myocardial infarction. -Postoperative irradiation in breast cancer treatment. -Steroid treatment of acute hepatitis.
D-Methodology: Formulation of meta-analysis includes qualitative and quantitative techniques. -Qualitative aspects include: a-Developing the research question to be analyzed. b-Reviewing the literature for relevant clinical studies. c- Evaluating the studies to identify similarities or to explain differences among them. d-Select the best clinical outcome. -Quantitative aspects include: Statistical analysis of the results.
What type of study to :chose depends on
what is the research question/ objective Time available for study Resources available for the study Common/rare disease or production problem. Often there are multiple approaches which will all work Choosing an established design gives you a huge head start in design, analysis and eliminating biases
Ethics of clinical studies :
Ethics of clinical studies concern the balance between risks and benefits of individuals who participate as subjects in research studies.
Protection of human rights :
Any person who is requested to consent to participate as a subject in a research study has the right to :
Be informed of the nature and purpose of the experiment . -Be informed about the steps to be followed in the experiment . Be informed of any attendant discomforts and risks to be expected from the experiment . Be given an explanation of any benefits to the subject to be expected from the experiment . Be informed of medical treatment to the subject after the experiment if complication arise .
Be given an opportunity to ask any questions concerning the experiment or the procedures involved . Be instructed that consent to participate in the medical experiment may be withdrawn at any time , and the subject may discontinue participation in the experiment without prejudice. Be given a copy of a signed and dated written consent form when one is required Be given an opportunity to decide to consent or not to consent to a medical experiment without the intervention of any element of force .
For each case history described below, select the study design it most appropriately illustrates. A-Case report B-Case- control study C-Clinical trial D-Cohort study F-Case series report
A total of 300 newly diagnosed patients with laryngeal cancer are allocated to treatment with either surgical excision alone or surgical excision plus radiation treatment.
Patients admitted for carcinoma of the stomach are age –and sex – matched with fellow patients without a diagnosis of cancer and surveyed as to smoking history to assess the possible association of smoking and gastric cancer
-A 39 years old man who presents with a mild fever, sore throat, malaise, and headache is treated with penicillin for presumed streptococcal infection. He returns after a week with hypotension, fever, rash, and abdominal pain. He responds favorably to chloramphenicol, after a diagnosis of Rocky Mountain spotted fever is made.
A total of 3500 patients with thyroid cancer are identified and surveyed by patient interviews regarding past exposure to radiation.
A total of 3000 elderly people living in Tanta city were identified and followed up for one year to determine the frequency and risk factors for falls among elderly people.
In a prospective study, 500 children were followed up for 20 years to assess the risk for thyroid cancer. 100 children were exposed to radiation of neck ,and from this group, 7 subjects developed thyroid cancer. Also 3 subjects developed thyroid cancer from the non- exposed group.Calculate the incidence rate(I R) and the relative risk (R R) for thyroid cancer.
In Pediatric Department Tanta University, the staff decided to determine the percentage of medication compliance among epileptic children attending the out patient clinic for follow up and obtain their medicine. How would design a study to achieve this objective?
There is evidence that lead exposure has a significant effect on children intellectual abilities and academic performance. How would you design a study to examine this effect of lead on a primary school children in Tanta city?