Professional Documents
Culture Documents
Zikria, Ph.D.
Assistant Prof. Pharmacy Practice (BZU)
Re~Search
Research is an ongoing process of hypothesis generation,
refutation, refinement, and corroboration
Studious inquiry or examination; especially : investigation
or experimentation aimed at the discovery and interpretation
of facts, revision of accepted theories or laws in the light of
new facts, or practical application of such new or revised
theories or laws
A detailed study of
a subject, especially in order to discover (new)
information or reach a (new) understanding
Any gathering of data, information and facts for the
advancement of knowledge
“Research is a systematized effort to gain new
knowledge.” (V. Redman and A.V.H. Mory)
Bio-medical Behavioral
Health services
Research Design
The research design refers to the overall strategy or protocol that
the investigators choose to integrate the different components of
the study in a coherent and logical way, thereby, ensuring they
will effectively address the research problem and translate the
conceptual hypothesis into an operational one; it constitutes the
blueprint for the collection, measurement, and analysis of data.
Most problems in studies are due to poor design not poor analysis
When I came to practice I was looking for answers like everybody
else. For years I asked "what's the right answer?" Now I am
learning "What is the right question?“
Science is the holding of multiple working hypotheses
A study is only as good as its hypothesis
Admittedly, creative action can never be fully explained.
Case report
Epidemiology
Descriptive Qualitative
Before-After
Quantitative
Case-Crossover
Case series
Study Case-Control
Designs Non-Experimental
Ecologic
Cohort study
Analytic Parallel
Cross-sectional
Blinded
RCT
Experimental Non Blinded
Non-RCT
15 Cross Over
Types of Research Designs
Cross-sectional
Data are collected from the population on a single point or period only
Retrospective
Information usually relates to previous events
Prevalence
Cross-sectional studies collecting data relating to current situations or events to be occurring in a particular population
Incidence
Measure of the probability of occurrence of a given medical condition in a population within a specified period of
time.
Observational
Comprises of descriptive, often frequency analysis of cross-sectional data area
Prospective
Relating to future events
Exploratory
Commonly employ qualitative methodology and/or a mixture of approaches and methods
Hypothesis generating
Gives clues about important factors that may influence the behavior of individuals or success of service of explain a
phenomena
Longitudinal
Study follows up a sample of individuals or cases over a period of time
Cohort
A group of individuals is followed for a given period
Experimental study
To test a hypothesis (RCT)
Quasi-experimental design
If randomization is not possible (participants will necessarily be aware of the group they are in)
Feasibility study
Small scale studies
Aims to assess aspects of the efficacy or practicalities of an intervention
Involves small number of selected settings and often focus on specific features of the service that would be
deemed essential for its success
Case-control study
Hypothesis generating or hypothesis testing
Identification of causative factors or explanatory variables that lead to a particular outcome
Case-study
Focuses on a single case or a small number of cases in order to examine phenomena of interest
Pilot Studies
Small studies that are designed to test the methods, procedures, instruments and documentation
for a larger study to check the project feasibility
Triangulation
Studies combine different approaches, method and / or data within a single research study to provide
different perspectives on a set of issues related to the study aims and objectives.
Antimicrobial Resistance in Pakistan
Quantitative Research
Quantitative methods emphasize objective
measurements and the statistical, mathematical, or
numerical analysis of data collected through polls,
questionnaires, and surveys, or by manipulating pre-
existing statistical data using computational
techniques.
High proportion of published papers
Quick and cheap
Methodological rigour
Robustness
FINER- Feasible, Interesting, Novel, Ethical, Relevant
Research Objectives
Views, beliefs and attitudes
Generalization
Quantify
Casual relationship between variables
Proving or disproving a hypothesis
Components of a Study Protocol
Element Purpose
Research questions What questions will the study address?
Descriptive
Relational – Variables
Causal – Inference
Hypothesis
Null – No relationship
Alternative – Significant Diff
Significance (background) Why are these questions important?
Design How is the study structured?
Time frame
Epidemiologic approach
Subjects Who are the subjects and how will the be selected?
Selection criteria
Sampling design
Variables What measurements will be made/recorded?
Predictor variables
Confounding variables
Outcome variables
Statistical issues How large is the study and how will it be analyzed?
Hypotheses
Sample size
Analytic approach
Study Design
Cross-sectional on a single occasion
detects point prevalence; relative conditions, feasible; quick; economic;
allows study of several diseases / exposures, useful for estimation of the
population burden, health planning and priority setting of health problems.
Longitudinal
powerful, no temporal ambiguity; several outcomes could be studied at
the same time; suitable for incidence estimation, expensive; time-
consuming; inefficient for rare diseases
Cross-sectional survey for retrospective data
Retrospective Cohort
Repeated Cross-sectional
Experimental
planned, stronger evidence, valid results, controlled environments, less
common
Non-experimental descriptive designs
hypothesis generating
Populations
Doctors
Practitioners
Pharmacist
Physicians
Patients
Pharmacy Clients
Public
Policy Makers
Others
Settings
Hospital
Pharmacy
Community
Clinics
Others
Administration of survey
Written
Mail survey
Oral survey
Self-administered survey (supervised & unsupervised)
Group-administered survey
Interviewer-administered survey
Drop-off survey
Oral
Electronic
Sampling Procedures
A sample is “a smaller (but hopefully representative) collection
of units from a population used to determine truths about that
population”
Why sample?
Resources (time, money) and workload
Gives results with known accuracy that can be calculated mathematically
The sampling process comprises several stages:
Defining the population of concern
Specifying a sampling frame, a set of items or events possible to measure
Specifying a sampling method for selecting items or events from the
frame
Determining the sample size
Implementing the sampling plan
Sampling and data collecting
Reviewing the sampling process
Probability Samples
Probability Samples: each member of the population has a
known non-zero/equal probability of being selected without
bias
Random sampling- purest form, use software, draw directly from
the columns.
Multistage Sampling
Nonprobability Samples
Nonprobability Samples: members are selected from the
population in some nonrandom manner
Convenience sampling- easily accessible, exploratory research for
inexpensive approximation, preliminary research
Opportunistic Sampling
Sample Size
Sample Size (n) is the number of individuals in a group under study.
The larger the sample size, the greater the precision.
For statisticians, an n > 30 is usually sufficient for the Central Limit
Theorem to hold so that normal theory approximations can be used
for measures such as the standard error of the mean.
However, this sample size (n = 30) is unrelated to the clinicians’
objective of detecting biologically significant effects, which
determines the specific sample size needed for a specific study.
Choosing a sample size is to be done by combination of logistical
and pragmatic considerations which include:
(a) The number of subjects who can be recruited in the given time
period within available resources, and
(b) The final figure calculated must represent the minimum number of
subjects required to procure a reliable answer to the research question.
“What size sample do I need?”
The answer to this question is influenced by a number
of factors
purpose of the study
population size
the risk of selecting a “bad” sample
allowable sampling error
type of outcome i.e. proportions, mean, rates
Confidence intervals and their corresponding multiplyin
factors, based on the normal distribution
Criteria
Level of Precision or Sampling Error
This is the range in which the true value of the population is estimated
to be (i.e. ±5%). Sampling error is reduced when the study size
is increased and vice versa.
Confidence or Risk Level/Interval
This is based on Central Limit Theorem, if a 95% confidence level is
selected, 95 out of 100 samples will have the true population value.
The larger the sample size, the narrower is the confidence interval.
The multiplying factor 1.96 is used when calculating the 95 percent
confidence interval.
Degree of variability in the attributes being measured
The more heterogeneous a population, the larger the sample size
required to obtain a given level of precision. Proportion of 50%
indicates a greater level of variability than either 20% or 80%. 0.5 is
often used in determining a more conservative sample size.
Strategies for Determining Sample
Size
Studies that are too small may fail to detect important effects on the
outcomes of interest, or may estimate those effects too imprecisely.
If the sample size is larger than what is needed, the study will
become cumbersome and ethically prohibitive. Apart from this, the
study will become expensive, time consuming and will have no
added advantages.
If the study is well designed with a desired sample size then the
standard error will be less and the power and precision will be
good. All statistical procedures become valid in this context.
Inferential statistics has two parts: estimation of population
parameter in prevalence/descriptive studies and testing of
hypothesis for cohort/case control/clinical trials.
There are several approaches to determining the sample size.
Using a Census for Small Populations
One approach is to use the entire population as the sample.
Although cost considerations make this impossible for large
populations, a census is attractive for small populations
(e.g., 200 or less).
A census eliminates sampling error and provides data on all
the individuals in the population.
In addition, some costs such as questionnaire design and
developing the sampling frame are “fixed,” that is, they will
be the same for samples of 50 or 200.
Finally, virtually the entire population would have to be
sampled in small populations to achieve a desirable level of
precision.
Using a Sample Size of a Similar Study
Another approach is to use the same sample size as
those of studies similar to the one you plan.
Without reviewing the procedures employed in these
studies you may run the risk of repeating errors that
were made in determining the sample size for another
study.
However, a review of the literature in your discipline
can provide guidance about “typical” sample sizes that
are used.
Using Published Tables
These sample sizes reflect the number of obtained
responses and not necessarily the number of surveys
mailed or interviews planned
This number is often increased to compensate for
nonresponse.
Sample sizes in Table 2 presume that the attributes
being measured are distributed normally or nearly so.
If this assumption cannot be met, then the entire
population may need to be surveyed.
Equation 5 was used to calculate the sample sizes in
Table 1 and Table 2
Using Formulas to Calculate a Sample
Size
Although tables can provide a useful guide for
determining the sample size, you may need to calculate
the necessary sample size for a different combination
of levels of precision, confidence, and variability.
The fourth approach to determining sample size is the
application of one of several formulas
Formula For Calculating A Sample For
Proportions
For populations that are large, Cochran developed the
Equation 1 to yield a representative sample for
proportions.
n0 = sample size
Z2 = 1 – α equals the desired confidence level, e.g., 95%
e = desired level of precision
p = estimated proportion of an attribute that is present in
the population
q = 1-p
Z = found in statistical tables which contain
Development
Develop by yourself
Develop by others
Modifications/Additions
Variables
Population descriptors
Components of the attributes of interest
Validity
The validity of an instrument is the extent to which it
actually measures what it is designed to measure.
Accuracy
Testing the instrument
Types
Face Validity
Prima facia
Uncover obvious problems
Co-researcher , Other researcher, Blind, People from population
Criterion Validity
Correlate with other measures
Compared with established method e.g other instrument or
biomarker
Construct Validity
Corresponds to what is understood by a construct or concept
Socioeconomic and ethnic groups
Individual self perceived identity
Minority, racism
Health status, QOL, Satisfaction (facet-free vs facet-specific)
Content Validity
Covers all the relevant issues
Preliminary fieldwork
Qualitative enquiry
Exploratory/Semi structured interview
Focus groups
Nominal Group Techniques & Delphi Methods
Published Work
External validity
Generalizability
Applied to individual beyond the sample
Probability sampling technique, adequate sample size, good response rate
Reliability
Reproducible
Internally consistent
Split-half method
Cronbach’s alpha
Test Retest
Factor analysis
No ambiguity of question wording
Less reliable if retrospective
Recall events- Diaries
Too many intervals- less reliable scale
Test-retest- respondents are less consistent
Survey instrument can be reliable but not valid, it can not
be valid if it is unreliable
Sample
Power calculation
Smaller the sample size larger the CI.
RaoSoft
PS software
Danielle’s/Daniel formula
Cochrane formula
Power analysis
Statistical Procedures
Nominal ordinal
Ordinal Data
Continuous Data
Non parametric test
Parametric test
Correlation
Chai Square
Missing data
Regression
OR, RR
etc
p-value
While a small p-value can be interpreted as evidence for a real
difference between the groups, a larger ‘non-significant’ p-value must
not be interpreted as indicating that there is no difference.
It merely indicates that there is insufficient evidence to reject the null
hypothesis, so that there may be no true difference between the
groups.
Result is called statistically significant if it has been predicted as
unlikely to have occurred by chance alone.
Null hypothesis refers to a general or default position: that there is no
relationship between two measured phenomena, or that a potential
medical treatment has no effect.
In the significance testing approach of Ronald Fisher, a null
hypothesis is potentially rejected when the p-value turns out to be
less than a certain significance level, often 0.05
If your values is 0.005, there is only a 0.5% chance of that result
occurring due to chance.
One sided and Two sided tests
If it is accepted that the null hypothesis is false,
that means alternate hypothesis is true.
If the claim is about superiority of a new drug, this is a
one-sided alternative.
If the claim is not of superiority or inferiority but only that
they are different, the alternate hypothesis is two sided.
Wrongly rejecting a true null hypothesis is called
type I error and vice versa.
Qualitative Methodology
Structured
Also known as a standardized interview or a researcher-administered interview.
The interview is presented with exactly the same questions in the same order.
The answers can be reliably aggregated.
The comparisons can be made with confidence between sample subgroups or
between different survey periods.
Unstructured
Also known as non-directive interview.
Questions are not prearranged.
These non-directive interviews are considered to be the opposite of a structured
interview.
Semi-structured
Loose structure
Open ended questions
Flexible agenda
Serves as check list
Liberty to pursue questions in depth
Probing approach
Opportunity to clarify ambiguous replies
Sampling procedures
Purposive samples
Relevant to study
Most informative
Ensure variability
Representative samples
Quota from all centers
Convenience samples
Accessible
Unrepresentative
Theoretical samples
Data Collection
Interviews
Focus Groups
Observations
Written descriptions of observations such as field notes,
and reflections, ideas and conjectures
Transcripts
Narratives
Audiotaped
Transcribed verbatim
Contextual data
Paraphrasing of the response
Data processing & Analysis
Organize into themes
Analytical procedures
Computers
Reporting of results
Validity
Communicative validation
Researcher returns to the field to collect additional data to verify or further develop their findings.
Argumentative validation
An attempt is made to use the dataset to argue a contradictory viewpoint.
Cumulative validation
The researcher uses the literature to demonstrate how their findings are consistent with existing knowledge of the
subject.
Reliability
Maintaining meticulous records of the interviews and observations
through documenting the process of analysis in detail.
Generalizability
Theories
Phenomenology
Cyrandeal theory
Discourse analysis
Mix Methodology
The integration of both Qualitative and Quantitative methodologies
broadens the perspective of a research and unravel the complexity of many
different factors that influence health.
Concurrent design
Compare and validate data collected from both methods.
Usually the same individuals provide both the qualitative and quantitative data.
Sequential design
The first one informs the analysis of the second.
A preliminary qualitative study may precede a large quantitative study.
Qualitative method provides complementary assistance to the quantitative
research.
For Example: Findings from in-depth interviews and focus group discussion could be used to
develop the content of questionnaire (to include important topics and
improves the effectiveness of the survey.
Epidemiological studies
Non-interventional
AKA observational studies
Researchers do not manipulate situations/objects
Only describes or analyses situations/objects
Interventional
Participants are assigned to receive one or more
interventions (or no intervention) so that researchers can
evaluate the effects of the interventions on biomedical or
health-related outcomes.
Non-interventional studies
Descriptive studies
Case series
Community diagnosis or need assessment
Epidemiological description of disease occurrence
Descriptive cross-sectional studies
Ecological descriptive studies
Analytical studies
Case-control studies
Cohort studies
Prospective cohort studies
Retrospective cohort studies
Analytical cross-sectional studies
Descriptive studies
When an epidemiological study is not structured
formally as an analytical or experimental study i.e.
when it is not aimed specifically to test a hypothesis, it
is called a descriptive study
Both groups should, at the outset of the study, be free from the
condition or conditions under consideration
Both groups are then observed over a specified period to find out
the risk each group has of developing the condition(s) of interest
Design of a cohort (prospective) study
Example of Prospective cohort study design
Design features
Selection of cohort
a community cohort of specific age and sex
an exposure cohort, e.g. radiologists, smokers, users of oral
contraceptives
a birth cohort, e.g. school entrants
an occupational cohort, e.g. miners, military personnel
a diagnosed or treated cohort, e.g. cases treated with radiotherapy,
surgery, hormonal treatment
No. of new No of
cases students
“at risk” at
the
begining
Admitted to the emergency room for an alcohol-related injury 400 3500
Unintended pregnancy? 252 2000
Diagnosed with depression? 310 3000
Obese? 543 2100
Person-time approach/incidence density
This approach is an improvement over the conventional
measure of incidence, because it takes into consideration
both the number observed and the duration of
observation for each individual
more treatment groups and the outcomes the groups are compared after
sufficient follow-up time.
Properly executed, the RCT is the strongest evidence of the clinical
PICO
influencing variables.
Outcome variables define and answer the research question and should have
outcome.
used).
A scientifically valid control population should be
comparable to the study population in important
patient characteristics and prognostic factors, i.e., it
should be as alike as possible except for the treatment
Randomization
Assurance that subject populations are similar in test and control
treatment.
Blinding is intended to minimize the potential biases
Phase I
Phase II
Phase III
Phase IV
Phase I clinical trial
This first phase in humans is preceded by
considerable research
short duration
Phase II clinical trial
Also carried out on volunteers selected according to
strict criteria
Purpose of Phase II is
to assess the effectiveness of the drug or device
to determine the appropriate dosage
to investigate its safety