PHILIPPINE REHABILITATION INSTITUTE FOUNDATION, INC.

College of Sciences

CLINICAL RESEARCH

Step 1: PROBLEM IDENTIFICATION & CLARIFICATION

1. Identify a research problem

2. Clarify the problem
3. State the research question properly

 What is a Research Problem?

- the starting point of any research activity

- central point of research
- may question about characteristics of events, knowledge which may have immediate application in
the solution of a problem
- may identify factors that may lead to the occurrence of an event

 in Medicine:
1. nature & characteristics of an event or phenomenon
e.g. anatomic structure
physiologic principle
biochemical pathway
pharmacologic action

2. relationship between 2 or more variables or events

e.g. precursor and product
exposure and outcome
cause and effect
intervention and result

 Question Form – best way to state your research problem

e.g. > Is there a relationship between socio-economic background and drug abuse?
> What is the magnitude and pattern of occurrence of coronary heart disease in Manila?
> Can continuous deworming eradicate ascariasis?

 RESEARCH comes from the word “reserche”, which means to search or investigate exhaustively

What is a good research problem?

1. Researchability – can be tested empirically, data can be collected to answer the question or resolve
the problem

a problem that requires value judgment cannot be resolved, e.g. Is induced

abortion immoral? Problem must be rephrased as, “What percent of the people
think or believe induced abortion is immoral?”

2. Significance – “the answer to the question matters”

 -it affects a large population
 -has serious morbidity consequences

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 -related to on-going projects

 -fills the gap in knowledge and technology
 -has practical application
 -will improve the practice in the profession

in short, the potential result is worth the effort, time and money that will be put into the research.

3. Feasibility – the methodology that will be required in answering the question must be feasible and
practical
 adequate subjects for the study
 procedures are technically possible
 information can be collected
 study can be completed within a reasonable period of time

 Other things to consider:

o CRITICAL MASS – problem is broad and large enough
o INTEREST – current interest in the problem

How is the RESEARCH PROBLEM or QUESTION formulated?

First, determine the TOPIC of INTEREST.

Identify the general topic and narrow it down to a specific topic or subject.

e.g. general - health problem in industry

specific – exposure to chemicals and effects

Second, determine if problem deals with:

a. Characteristics of event
e.g. are there adverse effects of working in the chemical industry?

b. Relationship between factor and event

e.g. does exposure to chemicals in the industry produce adverse effects?

Further, the investigation may need to determine if:

1. the antecedent factor has to be identified
2. the relationship of identified factor with event is to be verified
e.g. does exposure to lead cause adverse effects?

Third, refine the problem statement.

1. Write down the problem in question form. This helps in crystallizing the problem
2. Clarify what you really want to find out.
 use clear terms e.g. use effectiveness instead of benefits
use accuracy instead of useful

 be specific e.g. does long term exposure to chemicals to lead result infertility?

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After the IDENTIFICATION of the PROBLEM –

DISSECT and CLARIFY the problem by:

1. determine the various facts/components of a abroad problem
> each subcomponent should be researchable

e.g. the problem of the effectiveness of an immunizing agent

amount/level of protection desired or provided by the immunization
vehicle of the immunizing agent
mode, dosage and interval of administration
level of antibodies produced
immediacy and duration of effectiveness
adverse effects
2.a thorough literature review

Step 2: FORMULATION OF HYPOTHESIS

1. Differentiate the types of research hypothesis

2. Formulate logical hypothesis for a given problem

What is a HYPOTHESIS?

- is a suggested or tentative answer to the research problem in the form of DECLARATIVE SENTENCES.

e.g. > Socio-economic conditions and drug abuse are inversely related.
> The morbidity and mortality rates of CHD in Manila are moderately high.
> Continuous deworming can eradiate ascariasis.

 Why is it necessary to formulate a hypothesis?

 it provides the basis for STATISTICAL SIGNIFICANCE of the findings of the study
 it establishes the framework to approach the problem
 it helps in the determination of SAMPLE SIZE

TYPES of HYPOTHESIS

1. Null
e.g. The serum uric acid level of diabetics is not elevated.
Coffee drinking does not cause CHD.

2. Alternative or Positive Hypothesis

1. two-tailed or non-directional: does not indicate whether association is direct or inverse
e.g. Socio-economic conditions and drug abuse are associated
The serum uric acid level of diabetics varies from the normal values
2. one-tailed or directional alternative hypothesis: gives the direction of the association or
states which is greater when 2 samples are being compared

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e.g. Socio-economic conditions and drug abuse are inversely associated.

The uric acid level of diabetics is higher than normal.

 the SAMPLE SIZE required is smaller when the hypothesis is one-tailed.

When should each type of hypothesis be used?

1. Alternative or Positive Hypothesis is for testing risk and prognostic factors as well as an
intervention.
2. A one-tailed hypothesis is better than a two-tailed hypothesis
3. Null Hypothesis is for testing safety of drugs and other interventions, and “proving” that a health
or medical belief is a myth or erroneous.

What is the basis of your Hypothesis?

Begin by identifying the FACTORS which may have a relationship with the OUTCOME of INTEREST.

This FACTORS are identified through the analysis of existing DATA or STUDIES.

4 Approaches:
1. Method of Differences
2 populations -- low outcome: non-prevalent factors
--high outcome: prevalent factors

2. Method of Analogy
2 outcomes -- outcome of interest
--similar to outcome of interest – known causation

3. Method of Concomitant Variation

outcome of interest fluctuates with the factors factors may be causally related.

4. Method of Agreement
outcome distribution varies according to variables such as PERSON, TIME or PLACE.
look for factors that are variably distributed; these may be possible causes of the outcome.

 Then, the factor may be incorporated in the research question or subquestion which is restated in
a declarative sentence.

e.g. The incidence of coronary artery disease is five times in cigarette smokers than in non-smokers.
The efficacy of manual therapy in the treatment of MS conditions is 50% greater than that of the
traditional PT approach.

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Step 3: SETTING OF OBJECTIVES

1. Formulate research objectives

2. Identify relationship between different types of variables
3. Determine appropriate indicators for a scientific study

What are OBJECTIVES?

- aim/goal of an action or DIRECTION

- what the researcher expects to achieve
- it is the solution/s to the problem affirmation or negation

 Why are Objectives important?

 they give an indication of relevant variables
 they guide you in the research design or methods
 they tell you what data to collect
 helpful in PLANNING the results
 bases for the interpretation of results

Types of Objectives
1. General: overall purpose, derived from the broad statement of problem and hypothesis
e.g. problem – Is there a relationship between socio-economic background and drug abuse?
objective – To determine if there is a relationship…

2. Specific: specific outcomes of the study

e.g. problem – Is exposure to lead cause adverse effects?
Objective – To determine if exposure to lead…

Examples:
1. problem – Is there a relationship between socio-economic status and drug abuse?
general objective – To determine if there is a relationship…
specific objective – To determine the frequency of drug abuse by social class, level of education,
occupation, etc.
To determine the types of drugs used by the different social groups and by age,
sex, etc.

2. problem – What is the magnitude and pattern of occurrence of coronary artery disease in Manila?
general objective – To determine the pattern…
specific objective – To determine the prevalence and mortality rates of CAD by geographic
distribution in Manila, by personal characteristics such as sex, age, social
class, occupation, etc.
To determine the monthly mortality rate in Manila.

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 Characteristics of SPECIFIC OBJECTIVES:

o adequate to meet the main purpose >> specific objectives collectively should enable the
author to achieve the general objective
o clear statements which incorporate the specific hypothesis and specify the variables
o expressed in measurable terms in quantitative forms and variables are specified

 What are VARIABLES?

o characteristics of subjects, the outcome or results of a process, or factors that have some
influence on the subject of inquiry
o these are factors used to measure the event or changes in the event under study
o variables are either QUALITATIVE or QUANTITATIVE
 QUALITATIVE – not expressed numerically such as sex, civil status, etc.
 QUANTITATIVE – expressed numerically such as age, height and weight
i. Discreet – integers, whole numbers
ii. Continuous – whole, fractions
o INDEPENDENT variable – factor that affects the value of the dependent condition that
produces the outcome
e.g. cause and effect relationship  CAUSE
experiment  one being manipulated
o DEPENDENT variable – factor whose value is affected by the independent variable. It is the
outcome.
e.g. cause and effect relationship  EFFECT
indicator of change in the event
o CONFOUNDING variable – variable which is not the principal interest of the study, but distorts
the result of the study because it is associated with both the independent and dependent
variables
e.g. age and sex – if they are not the subject of investigation

 Variables must be defined in operational terms and not in conceptual or dictionary definitions.
Operational means the author should define the variable according to what it means in the
research which shall enable him to properly classify or categorize the subjects or any event.

Examples of Operational Definitions

Rheumatic Heart Disease – a person shall be labeled a case of RHD if he has both of the following:
** stenosis and/or insufficiency of the mitral and/or aortic valves
** history of rheumatic fever confirmed by the presence of carditis and/or migratory
polyarthritis, and an elevated ASO titer.

Obesity – an individual shall be considered obese if his weight is at least 10% in excess of his desired
body weight computed through a formula: --

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What is an INDICATOR?

- The computed or collated collective characteristics of the persons making up the study population
e.g. measurements – mean, variance and frequency distribution
counts – rates and ratios of disease occurrence such as incidence rate, prevalence rate
and death rate

Notes to Remember:
** specifying the variables helps in planning the data collection
** specifying the indicators guides data analysis

Step 4: CHOOSING THE APPROPRIATE RESEARCH DESIGN

What is a RESEARCH DESIGN

- plan/course of action the researcher takes to solve the research problem

- not the method of collecting date, but the STRATEGY or APPROACH
- the methods of the study: design, means of the data collection, methodology of process & analysis

Broad of Classification

1. DESCRIPTIVE – an inquiry into the nature of an unknown phenomenon or the occurrence of an event.
- seeks to know the characteristics of the phenomenon or event
- does not explain relationships but seek knowledge for better understanding
- aim is to infer to the reference population the findings from a sample

2. ANALYTIC – designed to test a hypothesis of relationships

a. OBSERVATIONAL – test hypothesis of relationships without artificial manipulation of the study
factors
a.1. Cross-sectional study in epidemiology or relate prevalence of independent variable
with prevalence of dependent variable
a.2. compare frequencies in those who have affected and who do have not the dependent
variable or outcome
- effect is manipulated; control study in epidemiology
a.3. compare occurrence of the dependent variable with & without the independent variable
under investigation
- cohort study in epidemiology
b. EXPERIMENTAL – one in which the researcher artificially manipulates the study factors
b.1. true experiment – allocation of factor is randomized (a sample representative of the
study population)
b.2. quasi experiment – no randomization

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How to plan a Research Design?

Basic considerations:
1. choice of study population
2. selection and classification
3. assessment of variables
4. processing & analysis of data

 for a Descriptive Research Design

- 4 steps to undertake:
1. choose your study population – people from a particular geograph: area, students, residents,
occupational
- patients with a particular illness
2. sampling – draw a representative sample
3. assessment of variables or collection of the data needed for the study
4. data analysis

 for an Analytic Research Design

1. Observational – test of hypothesis of relationship without artificial manipulation of study factors

a. CROSS–SECTIONAL STUDY: survey or prevalence study
how to plan the research design:
o first: choice of population – random sample from target population
o second: classification of subjects and assessment of variables – information is
that which exists during the survey
e.g. selected subjects are examined, observed & questioned about the
independent & dependent variables (the cause & effect, or the factor & the
disease or outcome status)
o third: computation of data collected to determine prevalence rates –
hypothesis of relationship between factor and outcome may be generated
b. CASE-CONTROL STUDY: compares the frequency of the factor among those with the
outcome and those without the outcome
steps:
o first: requires 2 populations – one with the outcome & another without the
outcome
e.g. if cases were selected from a hospital controls should likewise come from
the same hospital
o second: the cases and controls are questioned regarding the factor under
study; the study starts from the outcome & looks backward at the suspected
cause
o third: data analysis – the determination and the comparison of the frequency
of the factor in the subjects and the controls

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c. COHORT STUDY: to test the hypothesis of relationship by comparing the frequencies of the
outcome in those with the factor (exposed) and those without the factor (unexposed)
o first: selection of study population and do a preliminary screening
2 groups – those with the factor & those without the factor
o second: follow-up of subjects who might/will develop the outcome
through re-examination or surveillance (called a concurrent cohort study
or prospective cohort study) using primary data
*non-concurrent or retrospective cohort study – uses secondary data
(hospital records of the population which has been pre-classified)
o third: analysis of data – computation and comparison of frequencies of
occurrence of outcome and relative risk of developing the outcome

2. Experimental Research Design – the strongest of all the study designs because they provide the
most control over the study situation
o first step: same steps as the cohort study except that researcher chooses a
study population without or free of the factor or intervention
o second step: subjects are grouped into 2
- (+) intervention
- (-) intervention
 sampling should be randomized..if not randomized = Quasi experiment
o third step: detection of outcome
o fourth step: data analysis

How is an Appropriate Design Selected:

- the principal basis for selection of the design is the OBJECTIVE OF THE STUDY and the “state of the
art” (amount of knowledge & technology that have been developed so far)

1. to know more about the phenomenon  descriptive design

2. to determine the prevalence of the outcome in various groups and/or to examine relationship
between the factor and an outcomes based on prevalence data  cross-sectional study design
3. to test a hypothesis of relationship between variables, and there are not enough knowledge on the
subject, or the outcome/effect is rare  case-control
4. to test a hypothesis and there are already enough evidence that the hypothesis is likely to be true 
cohort study
5. to evaluate the efficacy/effectiveness of an intervention  experiment

- other considerations: technical feasibility, cost of the project, ethical issues

is the design technically workable?
can accurate data be collected?
is there fund for the design?

What are the Basic Requirements of each type of Research Design for the Findings to be Valid:

1. adequate number of subjects or observation

2. accurate and precise data

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Different Subject or Study Population requirements for a Research Design:

1. Descriptive: study population is the target population from which to draw your representative sample
2. Cross-sectional: same as descriptive; findings also apply to the target population
3. Case-control: study population is the entire or representative sample of the population with the
dependent variable (diseased population)..the control is the entire population or representative
sample of the population without the dependent variable (well population)
*confounding variables should be controlled
4. Cohort: comparability of the exposed and the unexposed group in all respects
- considers the influence of confounding variables
- does not require a representative sample of subjects from the general population
5. Experimental: same as cohort; comparability of the experimental and control groups through scientific
allocation of the factor/intervention

Summary
descriptive cross-section case-control cohort experimental
1. adequate sample size x x x x X
2. sample representative of x x - - -
target population
3. controls - - x x X
4. similarity of comparison - - - x x
groups

Sampling Techniques
- to obtain a representative sample methods

1. Random sampling – method of selecting a number of subjects (n units) from a population or universe
(N) such that every member has an equal chance of being drawn into the sample

2. Systematic sampling – method where every nth unit (such as every fourth or fifth member) is selected
from a population N which is arranged in some definite way to obtain a sample of units
e.g. 10 units to be selected from 50, 1 unit has to be selected for every 5 units.
the population is numbered 1 to 50 and the first unit is obtained at random from units 1
to 5, and every fifth unit thereafter.

3. Stratified sampling – the population is divided into subpopulation or strata..samples from each stratum
are then selected either by random or systematic sampling as if each stratum is a “population” by
itself
stratified random sampling
stratified systematic sampling
 to obtain optimum results, the sizes of the “population” should be allocation proportionately
e.g. stratum a is 10% of entire population – 10% of entire sample
stratum b is 15% of entire population – 15% of entire sample

4. Cluster sampling – when TIME, economy and convenience are not available, you can draw a sample
consisting of a group or cluster of similar units
e.g. instead of choosing 1000 houses at random, 20 blocks of 50 houses are chosen

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5. Multi-stage sampling – used for extremely large populations; sample in more than one stage
e.g. first stage sampling – select a sample (geographic)
selected first-stage sample – select a second stage sample & so on

Allocation of Factor or Intervention

- assignment of subject to the treatment and control
- used in experimental & control groups
- objective: to ensure equal distribution of variables that can confound the relationship between the
treatment and the outcome
- techniques:
1. Random Allocation – same principle as random sampling
e.g. place in a container equal number of envelopes/papers labeled 1, 2 or 3. for every
subject an envelope/paper is drawn to determine to which group he is to be assigned
2. Systematic Allocation – similar to systematic sampling; each subject is alternately assigned to the
treatment or control groups as they come or after they have been arranged in some definite way

*random allocation is preferred for equal distribution of confounding variables but leads to unequal
number of subjects
*systematic allocation assures equal numbers in the groups
*block randomization can achieve both objectives of equal chance and numbers

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