medical research methodology
TRANSCRIPT
Medical Research methodology
Dr. Waled Al-DubaiAssociate professor
Sana’a University1437-2016
Definition of researchResearch is a Systematic and an Organized
method to Finding Answers to QuestionsOR:
Research is a systematic investigation into a subject in order to discover new information or new fact or reach a new understanding or to collect information on a subject
Research consist of the previx Re which means ( again , or a new ) And Search (verb) means ( to examine, or to try )
Definition of research RESEARCH IS IS SYSTEMATIC
because there is a definite set of procedures and steps which you will follow in order to get the most accurate results.
Research is ORGANIZED because there is a structure of research
Definition of researchFINDING ANSWERS
Finding answers to a hypothesis or to the question of the research is the end of all research, because, research is successful when we find answers. Sometimes the answer is no association or no corelation or no significant differences , but it is still an answer.
QUESTIONS Question is central to research , because research with-out a question, has no aims .
The researcher Should be patientShould be ambitiousRemember it is research
Classification of Medical Research
Medical research 1-Primary research
Primary research is a research which involves the collection of data that does not yet exist
2-Secondary research Secondary research is a research which involves
the collection of data from studies of other researchers
Classification of Experimental Medical Research
Classification of Observational Medical Research
Notes1-Descriptive study is an observational study which
describes the distribution of characteristics of a disease or outcome, like percentage of (male ,
female) or (children, adult) in acute leukemia, …etc
2-Analytical study is an observational study which is looking for associations between exposure and outcome and analyze them for possible causes and effects by using case and control groups.
3-The best feature that distinguishes an analytic study from a descriptive study is a using comparison Group in analytic study
Descriptive study1-Case report ( on one patient)
Case reports often describe new case that cannot be explained by known diseases or syndromes or describe case that show an important variation of a disease or condition .
Advantages1-Can help in the identification of new syndrome or disease
2Help in detecting new drug side effects and (adverse or potential uses beneficial)
Disadvantages 1-Cases may not be generalizable
2-Not based on systematic studies(consider as non-resaerch by most epidemiologist .
3-Causes or associations may have other explanations
Example of case report Haemorrhagic-fever-like changes and normal chest
radiograph in a doctor with SARS. Wu EB1 ,Sung JJ.Lancet. 2003 May 3;361(9368):1520-1.
AbstractA 33-year-old doctor contracted severe acute respiratory
syndrome presenting with features of disseminated intravascular coagulopathy without changes in the chest radiograph initially. A CT scan of his chest showed marked lung changes. His condition improved with intravenous methylprednisolone 500 mg daily and ribavirin 1.2 g orally thrice daily. The case illustrates the importance of a break in fever between the viraemic and lung inflammatory phases of the illness that occurs before radiographic changes and which may obscure diagnosis. Careful quarantine and follow-up of these patients are necessary. Coagulopathy is usually uncomplicated and early CT of the chest may elucidate
hidden lung changes and facilitate a rapid diagnosis.
2-Case series Case series are the same of case report in
advantages and disadvantages but Case series are collections of different case reports of different patients of the same case or condition or
disease or syndrome .
3-Discreptive cross-sectional study
A descriptive cross-sectional study may be purely descriptive and used to assess the prevelance and distribution of a particular disease in a defined population,It also called prevalence study or Cross-sectional survey They may cover, for example:
1-Physical characteristics of people (weight, height), or the environment (everything about environment , like temperature), as in
a- prevalence surveys (of bilharzia, leprosy, HIV) ,b- evaluation of coverage of immunization,
2-Socio-economic characteristics of people such as their age, education, marital status, number of children and income,
If a cross-sectional study covers the total population it is called a. census
.
3-Discreptive cross-sectional study
Adventage1-provides snap shot about outcome
2-Simple and quick3-Is first line of epidemiological research4-It estimates the prevalence of disease
Prevalence is the total number of new and old cases in defined population
5-Good for common and chronic diseases(hypertension, diabetes)
Disadventage1-We can not establish causality because we do not know
whether the agent causes the outcome or not (We do not know who come first)
Example of descriptive cross sectional study
Type II Diabetes Mellitus and impaired glucose tolerance in Yemen: prevalence, associated metabolic changes and risk factors
Al-Habori M1 ,Al-Mamari M ,Al-Meeri A
Diabetes Res Clin Pract. 2004 Sep;65(3):275-81.
AbstractOBJECTIVE :
To investigate the prevalence of type II Diabetes Mellitus (DM) and impaired glucose tolerance (IGT) and identify the metabolic abnormalities and risk factors associated with these conditions in an urban city of Yemen.
RESEARCH DESIGN AND METHODS :Cross-sectional, population-based study investigating 498 adults (245 males and
253 females) aged 25-65 years. The 1999 modified World Health Organization criteria were adopted for the diagnosis of Diabetes Mellitus and IGT. A standard questionnaire was applied and blood lipids, blood pressure, body mass index (BMI) and waist/hip ratio (WHR) were determined.
RESULTS :The overall prevalence of type II Diabetes Mellitus was 4.6% (7.4% in
males and 2% in females). Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were found in 2% and 2.2% of the study population. Factors independently related to any abnormality in glucose tolerance, using logistic regression analysis, were sex, hyperlipidaemia, hypertriglyceridaemia, and hypertension; whereas sex and age related to DM. More than 80% of the type II diabetics were over the age of 40, 35% being hyperlipidaemic, 22% being hypertensive and 18% obese. Sixty percent of IGT subjects were hyperlipidaemic and 20% were obese. Approximately 78% of obese individuals (>/=30 kg/m(2)) had normal glucose tolerance.
CONCLUSION :The prevalence of type II DM and its potential increase reflected by the high
prevalence of obesity in normal glucose tolerance subjects in the Yemeni population constitutes a major public health problem.
Important NOTES1-Outecome means disease or dependent variable
2-Exposure means risk factors or independent variable3-Case : A person with the disease or outcome of interest .
4-Control:A person who does not have the disease or outcome.5-Independent variable is a variables which may cause or affect
the outcome ( disease or dependent variable) .e.g independent variable is smoking but the outcome or dependent variable is lung cancer.
6-Dependent variable is the outcome in the study which undergoes to the effect of independent variable.
7-Risk factor is any factor whose presence is associated with an increased risk of a
disease or condition
Notes1-Non-intervention study is study
(observational study) in which the researcher just observes and analyses researchable objects or situations but does not intervene;
2-Intervention study is study(Expermental study) in which the researcher manipulates objects or situations and measures the
outcome of his manipulations
Classification of Observational Medical Research
Analytical studiesAnalytical study is study attempts to
establish causes or risk factors for certain problems.
This is done by comparing two or more groups, some of which have or develop the problem and some of which have not
1-Analytical comparative Cross-sectional study
Analytical comparative Cross-sectional study investigate the association between the putative risk factors and the outcome in the same time by both describing and comparing between
groups .
Example of analytical comparative cross- sectional study
Prevalence and factors associated with low birth weight in Axum and Laelay Maichew Districts, North Ethiopia:A comparative cross sectional study
Negassi Teklehaimanot1, Tesfay Hailu2, Huruy Assefa2* ,
International Journal of Nutrition and Food Sciences
2014:3(6:)560-566
Differences between descriptive cross-sectional study and analytical comparative cross-sectional study
Descriptive cross-sectional study1-Collected number of cases and number of total
population.2-Can assess only prevalence of disease or other
health eventsAnalytical comparative cross-sectional study
1-Exposer and outcome are assessed at the same time by using compare groups
2-Can determine association between exposure and disease by using
Prevalence odds ratio
Analytical studyCase Control Study
Case control study is a retrospective study which compares patients who have a disease or outcome of interest (cases) with persons who do not have the disease or outcome (controls), and looks back retrospectively to compare how frequently the exposure to a risk factor is present in each group to determine the relationship between the risk factor and the disease.
Case-control studies have been called retrospective studies because the investigator is looking backward from the disease to a possible cause(exposure)
Case Control StudyCase control studies are observational because no
intervention is attempted and no attempt is made to alter the course of the disease. The goal is to retrospectively determine the exposure to the risk factor of interest from each of the two groups of individuals: cases and controls. These studies are designed to estimate odds ratio which determine the association between risk factors and outcome .
Case control studyAdvantages
1-Good for studying rare conditions or diseases 2-Less time needed to conduct the study because the
condition or disease has already occurred 3-Help you to look at multiple risk factors
5-Useful as initial studies to establish an associationDisadvantages
1-Retrospective studies have more problems with data quality because they depend on memory (recall bias) .
2-Not good for evaluating diagnostic tests because it’s already clear that the cases have the condition and the controls do not
3-It can be difficult to find a suitable control group
Odds ratioOdds ratio is the odds of disease in individuals
exposed and unexposed to a factor.)Example :DDT (insecticide) and breast cancer
Interpretation of odds ratio
1-If odds ratio is = 1, this mean, there is no association between risk factors and outcome.
2 -If odds ratio is > 1, this mean, the exposure or the risk factor may increase the risk of occurring of the outcome or disease. From previous example,
persons who exposed to DDT could be more likely to develop Lung cancer by 3.7 times than unexposed group.
3 -If odds ratio is < 1, this mean, the exposure or the risk factor may decrease the risk of occurring of the outcome or disease (protective effect).
CASE-CONTROL EXAMPLEPROTECTIVE EFFECT OF GREEN TEA ON THE
RISKS OF CHRONIC GASTRITIS AND STOMACH CANCER
Veronica Wendy SETIAWAN1, Zuo-Feng ZHANG1*, Guo-Pei YU2, Qing-Yi LU3, Yong-Liang LI4, Ming-Lan LU5, Ming-Rong WANG6,Chun Hua GUO6, Shun-Zhang YU7, Robert C. KURTZ8 and Chung-Cheng HSIEH9
Int. J. Cancer: 92, 600–604 (2001)
Case control exampleAbstracts
Despite the declining trend, stomach cancer remains the second most common cancer worldwide. We examined the role of green tea consumption on chronic gastritis and stomach cancer risks. A population-based case-control study was conducted in Yangzhong, China, with 133 stomach cancer cases, 166 chronic gastritis cases, and 433 healthy controls.Epidemiologic data were collected by standard questionnaireand odds ratios (OR) and 95% confidence intervals (CI) wereestimated using logistic regression models in SAS. Inverse association was observed between green tea drinking and chronic gastritis and stomach cancer risks. After adjusting forage, gender, education, body mass index, pack-years of smoking and alcohol drinking,
ORs of green tea drinking were 0.52
3-Cohort Study In a cohort study , a group of individuals that is
exposed to a risk factor (called study group or case group) is compared to a group of individuals not exposed to the risk factor (control group). The researcher follows both groups over time and compares the occurrence of the outcome. Cohort study is called incidence study or follow up study, it is the best study of observational studies
Cohort study Advantage
1-used to determine incidence Incidence is the total number of new cases of
a disease) which occur during a specified period of time in a defined population
2-It shows that the exposure occurred first and the disease occurred second (temporality)
3 -Good for rare exposure 4 -Possible to study multiple outcomes
Disadvantages1-Take too much time, money and efforts
2 -Not good for rare diseases 3-Problem of non-response and drop-out
4 -Difficult to study multiple exposures 5-Ethical Issue may arise
Types of Cohort Studies
1-prospective cohort study Determine the exposure group and non-exposure
group and follow-up starts
2-Retrospective cohort study Both the exposure and outcome occurred in the
pastIt needs medical records
Measures the Association in Cohort study
Relative Risk (RR) or called Risk Ratio is the risk of getting the disease in the group with the risk factor divided by the risk of getting the disease in the group without the risk factor.
Interpretation of Relative Risk1-If Relative Risk is = 1, this mean, there is no
association between risk factors and outcome. Risk factor does not increase or decrease the risk of the disease.
2 -If Relative Risk is > 1, this mean, the exposure or the risk factor (predisposing risk factor) may increase the risk of occurring of the outcome or disease. Risk factor increase the risk of the disease. From previous example, persons who are obese could be more likely to develop diabetes mellitus type 2 by 2.4 times than unexposed group.
3 -If Relative Risk is < 1, this mean, Risk factor decrease the risk of the occurring of disease (protective factor)
RISK is the same as incidence rate
Cohort study exampleProspective Cohort Study of Green Tea
Consumption andColorectal Cancer Risk in Women
Gong Yang, Xiao-Ou Shu, Honglan Li, Wong-Ho Chow, Bu-Tian Ji,Xianglan Zhang, Yu-Tang Gao, and Wei Zheng
Cancer Epidemiol Biomarkers Prev 2007;16(6). June
Confounding factors
Confounding When an exposure and an outcome are
both strongly associated with a third variable .
Experimental studies(clinical trials) In Experimental study individuals are randomly
selected to at least two groups.One group is subject to an intervention (case ), or experiment, while the another group is not (control). The effect of the intervention is obtained by comparing the two groups
Experimental study gives the most reliable proof for causation
Randomized controlled Trial (RCT)
In this study we randomly distributes participants into an experimental group and a control group .
1-For example if the experimental group is HCV positive, we give them new drugs and the control group (HCV negative) we give them nothing or placebo ,
( placebo is a substance having no pharmacological effect)
And then we compare the result between the two groups and Measures of the association between the two groups like Cohort Study (Using relative risk (RR))
Exapmle22-For example, a researcher plans to study the effect of a
new drug. (The drug has already been tested extensively on animals and has been approved for trial use.) He plans to include 300 patients in the study who are currently receiving the standard treatment for the same condition for which the new drug has been designed. He explains the study to the patientsa sking their consent to be divided into two groups on a random basis. One group will receivethe experimental drug while the other group will continue to receive the standard treatment. He makes sure that the medications are disguised and labelled in such a manner that neitherthe research assistant administering them nor the patient know which drug is used. (This is called a double blind experiment.)
Randomized controlled Trial
Advantages 1-Good randomization will remove any population
bias 2-Easier to blind(mask) than observational studies 3-Populations of participating individuals are clearly
identified
Note :Clinical trial is look like cohort study but in clincal trials we have intervention but in cohort study we have observation
Randomized controlled Trial
Disadvantages 1-Expensive in terms of time and money
2-Loss to follow-up attributed to treatment
Example Vitamins C and E for prevention of pre-
eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial
McCance DR1, Holmes VA, Maresh MJ, Patterson CC, Walker JD, Pearson DW, Young
Lancet. 2010 Jul 24;376(9737):259-66
AbstractBACKGROUND :
Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the effect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes.
METHODS :We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised
placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks' and 22 weeks' gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive 1000 mg vitamin C and 400 IU vitamin E (alpha-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratified by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defined as gestational hypertension with proteinuria. Analysis was by modified intention to treat. This study is registered, ISRCTN27214045.
FINDINGS :Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment
groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70) groups (risk ratio 0.81, 95% CI 0.59-1.12). No adverse maternal or neonatal outcomes were reported
Secondary Research 1-A systematic review is a study which
provides a comprehensive review of all relevant studies on a particular clinical or health-related topic/question. The systematic review is created after reviewing and combining all the information from both published and unpublished studies .
1-A systematic reviewAdvantages
1-Coparhensive review of the current literature and other sources (unpublished studies, ongoing research)
2-Low coast Disadvantages
1-Very time-consuming 2-May not be easy to combine studies
Secondary Research 2-A meta-analysis is a statistical approach to
combine the data derived from a systematic-review. Therefore, every meta-analysis should be based on an underlying systematic review, but not every systematic review leads to a meta-analysis
meta-analysisAdvantages
1-Has Greater statistical power 2-Confirmatory data analysis
Disadvantages 1-Difficult and time consuming to identify
appropriate studies
