Dr khamis Elessi BSc, MD, MSc, DipAcu

Palestinian Board in Rehab. Medicine

Introduction to Research

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What is Research?Re (again) + SearchA highly intellectual activity used

during nature & matter investigation and deals specifically with the manner in which data is collected, analyzed and interpreted.

WHO - Research: A quest to gain knowledge through diligent search or investigation or experimentation (systematic process of collecting & analyzing data) aims to discover and interpret new knowledge.

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The honest research tutors

“I keep 6 honest & serving men with me,

They taught me all I know in life,

Their names are What and Why and

When and How and Where and Who”

Rudyard Kipling-1903

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Researcher has to see what every one else has seen and to think what no one else has thought.

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Objectives of researchTo provide answers for questions like

what, where, when, how and why.To bring out information that might not

be discovered in ordinary course of lifeTo verify existing theories and facts.To enable us to predict future eventsTo establish relationships & derive

explanationsTo help develop new tools,

generalizations and theories to certain phenomenon

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Characteristics of Research

Requires expertise & skills necessary for

research.

Characterized by patience and unhurried

activity.

Starts with a specific question or

hypothesis.

Requires a clear objectives and

standardized steps plan

Requires certain method of data

collection and interpretation

Must be carefully collected, recorded and

reported.

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SIGNIFICANCE OF RESEARCH

It is needed for better decision

making

It sheds light on risks and

uncertain things

It identify alternative course of

action

It helps in economic allocation of

resources

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Includes too much Statistics & Calculations

Takes time

Useless

Only Theoretical

Just an academic exercise

Pays more Money

Too Difficult

(Sakesan Tongkhambanchong, )

Misconception about Research

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Types of Research

Classified from 3 main perspectives

1. Application of research studies (pure or applied research)

2. Objectives in undertaking the research (descriptive, correlational, explanatory or exploratory research)

3. Inquiry mode employed & end results (qualitative or quantitative research)

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Types of Research

From the viewpoint of researcher

Application Objectives Inquiry mode

Pure research

Applied research

Descriptive research

Exploratory research

Correlational research

Explanatory research

Quantitative research

Qualitative research

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Pure or Basic or Fundamental Research

Pure or basic or fundamental researchcarried out to increase understanding of

fundamental principlesThe end results have no direct or

immediate healthy benefits. basic research can be thought of as

arising out of curiosity. However, in the long term it is the basis for many commercial products and applied research. 11

Applied Research

research that is applied, accessing and using some part of the research communities' (think banks) accumulated theories,

knowledge, and techniques are often driven by state, commerce or clients.

(solar energy, water purification system,

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Types of Research

From the viewpoint of

Application Objectives Inquiry mode

Pure research

Applied research

Descriptive research

Exploratory research

Correlational research

Explanatory research

Quantitative research

Qualitative research

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Descriptive Research

Attempt to systematically describe a situation, problem, phenomenon, service or program,

Provide information about behavior or situations (Ex. the living conditions of a community), or describes attitude towards an issue (elections, favoritism etc.…)

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Examples of Descriptive research Aim

Socioeconomic characteristics of residents of a community

To describe what is prevalent about:-A group of people-A community-A phenomenon-A situation-A program-An outcome

Attitudes of students towards quality of teaching

Types of service provided by a hospital

Needs of community

Consumers’ likes and dislikes regarding service

Attitudes of nurses towards death and dying

Attitudes of workers towards management

Strategies to increase productivity of workers

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Correlational Research

To discover or establish the existence of a relationship/association/interdependence between 2 or more aspects/variables of situation

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Examples of Correlational research Aim

Impact of a program (medical/educational)

To establish or explore:- A relationship- An association- An interdependence

Relationship between stressful living and incidence of heart attacks

Impact of technology on employment

Impact of maternal and child health services on infant mortality

Effectiveness of marriage counselling service on extent of marital problem.

Impact of incentives on productivities of workers

Effectiveness of an immunization program in controlling infectious disease

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Explanatory Research

To clarify why and how there is a relationship between 2 aspects of situation or phenomenon

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Examples of Explanatory Research Aim

Why does stressful living result in heart attacks?

To explain:- why a relationship, association or interdependence exists

- why a particular event occurs

How does technology create unemployment/employment?

How do maternal and child health services affect infant mortality?

Why do some people have a positive attitude towards an issue while others do not?

Why does a particular intervention work for some people and not for others?

Why do some people adopt a program while others do not?

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Exploratory Research

To explore an area where little information is known.

To investigate the possibilities of undertaking a particular research study

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Types of Research

From the viewpoint of

Application Objectives Inquiry mode

Pure research

Applied research

Descriptive research

Exploratory research

Correlational research

Explanatory research

Quantitative research

Qualitative research

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Public Survey

Qualitative Research: descriptive, Emphasize on the depth of understanding and meanings, viewpoints and personal feelings.

Aims to generate theoretically richer observations. Wish to gain deep insight rather than make statistics.

Methods: Participant Observation, Unstructured Interview, Focus Groups.

Quantitative Research: quantifiable, Emphasize on precise, objectivity, and Generalizability .

Measure quantity or amount of something (phenomenon).

focus is on “how many? or “How often? How many think? Etc..

Results are expressed in numbers, percent or statistics. Methods: satisfaction questionnaire, surveys, census

data, election

Qualitative & Quantitative Research

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-Surveys:

A survey is designed to obtain information regarding the prevalence, distribution and interrelationships of variables within a population. In a survey, there is no experimental intervention. Surveys collect information on people’s actions, knowledge, intentions, opinions, attitudes, and values.

Survey data can be collected in a number of ways such as:

1. Face-to face interviews.2. Interviews by telephone.3. and self-administered questionnaires.

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Part 2Research Methodology

– Study designs

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What is Research Design?

A plan , structure, and strategy of investigation to obtain answers to research questions or problems

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Different Health Research Designs

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Epidemiological studies Can either be Descriptive or

Analytical (Explanatory).

Descriptive designs includes case reports, case series and descriptive studies

Analytical studies examine cause, efficacy, using the strategy of comparisons. They can be subdivided based on the behavior of the researcher whether he will just observe or experiment Observational designs Interventional (Experimental) designs

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Study Design Tree

Epidemiologic Studies

Descriptive

Case reports

Case Series

Descriptive studies

Analytical

Observational

Case-control

Cohort

Prospective

Retrospective

Cross-sectional

Intervention/Experi-mental

Randomized Trial

Study Types

Descriptive• Case report• Case series

Analytical or Explanatory

Observational• Cross sectional• Case-control• Cohort studies

Experimental• Randomized controlled trials

Strength of evidence for causality between a risk factor & outcome

TIME AND TYPES OF STUDYPAST

Case-controlFUTURE

CohortPRESENT

Retrospective ProspectiveCross-sectional

Time factor المقرر الوبائية الدراسة نوع تحديد في \ جدا مهم الزمن عنصر...تطبيقهاTime is important in determining the type of epidemiologic study to be done. If you are looking for relationship of cause and effect during present time, you will need a cross-sectional study. However, if you are looking at the cause and effect relationship on the past, you will need a retrospective study. If you looking at the relationships in the future, you will need a prospective study.

CASE REPORT/CASE SERIES

Case reports and case series describe the experience of a single patient or a group of patients with a similar diagnosis and a similar or different course of treatment.

In this design , you follow the subject and document all your data from their medical files and then describe what you notice and draw your conclusions

Case-control studyThe starting point of a case-control study is subjects with the disease or condition under study (cases). The cases’ history of exposure or other

characteristics, prior to onset of the disease, is recorded through interview and other sources.

A comparison group People without the disease (controls) are assembled, and their past history is recorded in the same way as for the cases.

The purpose of the control group is to provide an estimate of the frequency and amount of exposure in subjects in the population without the disease being studied. Whereas the cohort study is concerned with frequency of disease in exposed and non-exposed individuals,

The case-control study is concerned with the frequency and amount of exposure in subjects with a specific disease (cases) and people without the disease (controls).

Case-Control studiesCase-Control studies are usually but not

exclusively retrospective, the opposite is true for cohort studies.

The followings relate case-control to cohort studies:good for rare outcomes relatively inexpensivesmaller numbers requiredquicker to complete

Case-Control Design

1. Select group of subjects WITH disease/outcome of interest = CASES

Cases

2. Select group of subjects WITHOUT disease/outcome = CONTROLS

Controls

RF +

RF +

RF -

RF -

3. Measure (retrospectively) risk factors of interest.

4. Analyze using strength of association measures.

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Case-Control DesignAdvantages

1. not dependent on natural frequency of disease (study rare diseases)

2. well suited to study diseases with long latency

3. requires comparatively few cases (2:1 or 3:1 matching)

4. allows study of multiple potential causes of disease

5. relatively low cost and quick

6. ethical: disease has already occurred

Disadvantages

1. case selection may be problematic

2. controls may not be representative of population as cases in terms of disease risk or confounders

3. investigators may be biased when know of disease status of subjects

4. subjects may bias answers (recall) due to disease status

5. factors which are used to match are removed from analysis

6. incidence, prevalence, RR can't be calculated since no "population at risk" denominator is available

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Cross Sectional StudyConducted at a single point in time or

over a short period of time. No Follow-up.

Exposure status and disease status are measured at one point in time or over a period.

Called Prevalence studies allows comparison of prevalence among exposed & non-exp.

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Prevalence vs. Incidence

Prevalence

The total number of cases at a point in

time

Includes both new and old cases

Incidence The number of new cases over time

Cross Sectional Design

1. Select Pop of interest

Population of Interest

2. Select Sample

Study Sample

3. Assess population for both disease (outcome) status

Disease Positive

Disease Negative

RF +

RF +

RF -

RF -

and risk factor (exposure) status

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Cross-Sectional Design

Advantage:

1. Quick and Low Cost

2. Evaluate a large number of variables

3. Enroll a large number of Subjects

Disadvantage:

1. Subject selection may reflect selection bias (volunteers, hospital patients)

2. Is difficult to identify cause and effect relationship.

Common Uses:• Questionnaires and Surveys• to determine Prevalence not incidence• Hypothesis Development

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Cohort study Design (prospective)

Select two or more groups (cohorts) that are free of disease but differ on their exposure status. May start with one heterogeneous cohort

then divideCohorts have a “denominator” مقام

which allows the calculation of true risk rates.

Useful when “exposure” varies over time.

Cohort DesignAdvantages

1. allows risk to be expressed as incidence

2. certain biases are reduced:

exposure status

disease status

3. subject characteristics can be related to more than one outcome

Disadvantages

1. inefficient for studying rare disease

2. assessment of relationships limited to those defined at beginning of study

3. selection bias not controlled

4. loss to follow-up common

5. subjects may change w/regards to characteristics (exposure status)

6. expensive and time consuming

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Cohort Study Design1. Select Population of interest

Population of Interest

2. Recruit sample WITHOUT disease(s) of interest and measure risk factors

Disease Free Sample

(baseline exam)

Uses:

• Determining/quantifying risk factors• Establishing causality

Visit 2

3. Recall cohort periodically and re-measure risk factors and disease status

Visit 3 Visit n

Time

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Prospective cohort Study A prospective study watches for

outcomes, such as the development of a disease, during the study period and relates this to other factors such as suspected risk or protection factor(s).

The study usually involves taking a cohort of subjects and watching them over a long period.

The outcome of interest should be common; .

All efforts should be made to avoid sources of bias such as the loss of individuals to follow up during the study.

Prospective studies usually have fewer potential sources of bias and confounding than retrospective studies

Prospective cohort Study: Example

The water source in your town is contaminated with radioactive material due to explosion in a nuclear reactor.

A prospective cohort study is conducted, and the cohort is followed over time to determine if any illnesses occur in people who were exposed compared to people who were not exposed.

Relative risk needs to be calculated in order to determine the presence of an association between the radioactive material and the illness.

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Retrospective study designs A retrospective study looks backwards

and examines exposures to suspected risk or protection factors in relation to an outcome that is established at the start of the study.

Most sources of error due to confounding and bias are more common in retrospective studies than in prospective studies.

For this reason, retrospective investigations are often criticised.

In retrospective studies the odds ratio provides an estimate of relative risk.

You should take special care to avoid sources of bias and confounding in retrospective studies

Retrospective cohort Study- Example

In california, a previous train derailment resulted in a large chlorine spill. you suspect that the spill is having a residual impact on residents. It is necessary to know if people living within radius "X" of spill have a higher risk of respiratory symptoms than those living outside of "X." A random sample of town residents is categorized into an exposed group (within the "X" radius) and an unexposed group (outside the "X" radius). Then, they are asked about various respiratory symptoms they may be experiencing. Relative risk is calculated to determine if proximity to the spill is associated with current respiratory symptoms.

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2- Experimental/ Interventional Trials

Prospective , controlled experiment of human subjects to assess intervention for a specific disease. Asks an important research question, Clinical event or outcome Done in clinical or medical setting Evaluates one or more interventions compared with “standard treatment” Informed consent required

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Interventional STUDY

Animal experimentsDrug trialsHuman trials

Another area of the epidemiologic study is the experimental study.

Unlike analytical studies, in experimental studies, the researcher has control over the study subject’s activity.

These type of studies are usually applied in animals, drug trial and human subjects.

حرية له التجريبية الدراسات في الباحث فإن التحليلية الدراسات بعكس . و الحيوانات على تطبق عادة و المشاركين نشاطات في التحكم

اإلنسان على التجارب و الدوائية .التجارب

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Uses of Clinical Trails (experimental studies)

Test new drug therapy Test new surgical interventionsTest educational interventions

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Experimental Studies

Clinical trials provide the “gold standard” of determining the relationship between variables.

Random assignment determines each subject’s exposure

Allows direct estimation of incidence in exposed and non-exposed

Disease events of interest always occur after study initiation – prospective

Almost complete control of confounders Many variations (randomised, doulble

blinded , single blinded)

Randomized controlled trials Investigator controls intervention or

treatmentMajor advantage is ability to demonstrate

causalityEg. Effects of garlic on cardiovascular

disease prevention.

Disadvantages: not immune to bias: (non-compliance, incomplete follow-up, biased observation). may have low external validity

may not be feasible for studies of disease etiology (ethical considerations, rare disease) . may not be feasible for effective disease prevention exists. (can't withhold treatment). Can be very expensive

THE RANDOMIZATION PROCESS 1. Equal distribution of measured

characteristics in trial arms is optimized but never absolutely assured.

2. Randomization increases the likelihood that unmeasured variables are equally distributed between the two arms.

3. 3. Randomization in assigning the intervention promotes avoidance of bias.

 4. Ideally, the randomization scheme,

assignment is unknowable in advance. (Systematic sampling is knowable in advance, which is a limitation of this sampling system). 

5. Randomization applies to the individuals randomized, not to the groups actually receiving treatment or placebo. Therefore, analysis is always by intention to treat; no exclusions after randomization are allowed.

Steps in a randomized controlled trial

1. Select participants2. Measure baseline

variables3. Randomize4. Blinding the

intervention/exposure5. Follow subjects6. Measure outcome

Randomized Clinical Trial (RCT) Design

1. Recruit individuals WITH disease.

Study Sample

with disease

Randomization is essential, and with strict control of experimental conditions allows for minimal bias

Excellent internal validity (but possibly low external validity)

2. Randomize into treatment arms

Standard Treatment

New Treatment

Randomization

Outcomes

Outcomes

3. Follow up to assess outcomes after exposure or Intervention

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BLINDING

Blinding is not inherent to randomized trials, but should be used whenever possible as placebo effects are powerful.

Blinding requires placebo or use of alternate treatment that cannot be distinguished from treatment.

Single blinded: patient doesn’t know which arm any patient is in.

Double blinded: patient and person administering the intervention don’t know.

Triple blinded: patient, interventionist and data analyst don’t know.

Blinding

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Single blinding

Triple blindingDouble blinding

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Systematic Review? A "systematic review” comprehensively

locates, evaluates and synthesizes all the available literature on a given topic using a strict scientific design which must itself be reported in the review.

Aim of SR is: Systematic (e.g. in its identification of literature) Explicit (e.g. in its statement of objectives, materials

and methods) Reproducible (e.g. in its methodology and

conclusions)

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Why Systematic Reviews? Annually 3 million articles are published in

biomedical journals and biomedicine mass doubling time is less than 20 months.

You would need to read a dozen or more articles per day (365 days/yr.) to stay up to date.

Not all articles are valid or useful for patient care.

SR provide a summary and context of the current state of knowledge (that is lacking if you only read a few articles in an area).

Considered to be top level of evidence; everyone doing them

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Systematic Review: Structured review of the literature Set inclusion & exclusion criteria Assess study design quality Assess methodological quality Compile & summarize results

Main Goal: determine what the current evidence is on a specific topic for better decision making

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Systematic Reviews

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Systematic Reviews

Clear and focused study question Explicit definition of study criteria to be

included A priori protocol for collating the evidence Exhaustive search, including“hand-searching”

and unpublished studies Explicit or implicit factoring of study quality

It is the Most comprehensive resource for therapy Questions

Systematic reviews are characterized by:

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Systematic Review Killers

Low level research / Lack of Research

Heterogeneity of subject pools

Heterogeneity of methodology

Lack of detail prohibits comparison

Authors are often knowledgeable on topic & evaluation of study design & sources of bias, but not intervention methods

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Interventions for treating phosphorus burns (systematic Review) Barqouni L, Abu Shaaban N, Elessi K

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library

Meta-analysesMeta-Analysis:

Also a structured review of the literature

Set inclusion & exclusion criteria

Assess study design quality

Assess methodological quality (rarely)

Perform statistics on the integrated results of the grouped studies

Goal: draw conclusions from the results of the analysis of the grouped data

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Meta-Analysis: High-Dose Proton Pump Inhibitors Vs. Standard Dose In Triple Therapy for Helicobacter Pylori EradicationA. Villoria; P. Garcia; X. Calvet; J. P. Gisbert; M. VergaraAliment Pharmacol Ther. 2008;28(7):868-877.

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Meta-analysis

The prevalence and incidence of coronary heart disease is significantly increased in periodontitis: a meta-analysis.Bahekar AA1, Singh S, Saha S, Molnar J, Arora R.

Previous studies have shown conflicting results as to whether periodontitis (PD) is associated with increased risk of coronary heart disease (CHD). The aim of the current study was to evaluate whether such an association exists.

METHODS:A systematic review of the literature revealed 5 prospective cohort studies (follow-up >6 years), 5 case-control studies, and 5 cross-sectional studies that were eligible for meta-analysis. Individual studies were adjusted for confounding factors such as age, sex, diabetes mellitus, and smoking. The 3 study categories were analyzed separately. Heterogeneity of the studies was assessed by Cochran Q test. The studies were homogeneous; therefore, the Mantel-Haenszel fixed-effect model was used to compute common relative risk and odds ratio (OR).

CONCLUSIONS:This meta-analysis indicates that both the prevalence and incidence of CHD are significantly increased in PD. Therefore, PD may be a risk factor for CHD. Prospective studies are required to prove this assumption and evaluate risk reduction with the treatment of PD.

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