MPL 301 T

Research Methodology
Research

Oxford-
A detailed and careful study of something to find out more
information about it.

Merriam Webster-
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.
Scientific research
It is a systematic and organized process of
inquiry that aims to expand human knowledge
and understanding of the natural world or
various phenomena through-
• Observation
• Experimentation
• Data collection
• Analysis
• Interpretation.
Requirements-
• Hypothesis: Researchers formulate hypotheses, which are educated
guesses or predictions about a particular phenomenon based on existing
facts and figures. These hypotheses are then tested through
experiments or observations to determine their validity.

• Empirical Evidence: Scientific research relies on empirical evidence-

facts and figures, which means that it is based on observations and data
derived from previous experiments or observations of the real world.
Researchers gather data to test hypotheses and theories.

• Systematic Approach: Scientific research is conducted in a systematic

and structured manner. Researchers follow predefined validated
methodologies and protocols to ensure that their studies are
replicable/reproducible and can be subject to peer review.

Serendipity
• Infrastructure and resources- Scientific research requires adequate
infrastructure- GLP compliant lab, equipment, materials- raw materials,
human resources- trained and experienced personnel.

• Ethical Standards: Ethical considerations are essential in scientific

research. Researchers must adhere to ethical guidelines and principles,
including obtaining informed consent from participants, ensuring the
welfare of research subjects, and maintaining the confidentiality of data
and using others data (plagiarism).

• Objectivity : Scientific research aims to be objective and unbiased.

Researchers strive to minimize personal biases and emotions that may
influence their observations or interpretations. They use rigorous
methods and statistical analysis to draw conclusions.

• Communication: The results of scientific research are usually

communicated to the broader scientific community and the public
through publications in scientific journals, presentations at conferences,
and other forms of dissemination. Effective communication is crucial for
sharing knowledge and advancing science.
Practical difficulties in research
• Limited Resources: Research requires funding, equipment, access to
specialized facilities, and personnel. Securing adequate resources can
be a significant challenge.
• Time Constraints: Research can be time-consuming. Gathering data,
conducting experiments, and analyzing results may take longer than
initially anticipated.
• Data Collection Issues: Collecting high-quality data can be challenging.
Researchers may face difficulties in obtaining a sufficient sample size,
dealing with non-response or participant attrition, or ensuring data
accuracy and reliability.
• Technical Challenges: In some fields, researchers encounter technical
challenges related to equipment malfunctions, software errors, or data
storage and management issues.
• Unforeseen Variables: Researchers may encounter unexpected
variables or confounding factors that were not initially considered.
These can complicate data interpretation and analysis.
• Access and Permissions: Gaining access to certain populations,
locations, lab facilities or data sources can be difficult.

• Interdisciplinary Collaboration: Research that crosses disciplinary

boundaries may face challenges related to communication and
integration of diverse perspectives and methods.

• Data Analysis Complexity: Complex data analysis techniques may

require specialized statistical or computational skills. Researchers may
struggle with the complexity of analyzing large datasets or using
sophisticated analytical tools.

• Communication Barriers: Effective communication of research

findings to both peers and the public can be challenging. Researchers
may need to translate complex scientific jargon into accessible
language and formats.
• Publishing and Peer Review: Getting research published in reputable
journals and undergoing the peer-review process can be competitive
and time-consuming. Revisions and rejections are common. Open
access cost is very high.
 Types and Design of study
• Experimental Study-RCT and Non RCT

• Observation Study- Cohort, Case Control, Cross

sectional
 Study design
• Study designs are rationally planned methods considering the goal to
be achieved, that helps to derive a valid and meaningful scientific
conclusion using appropriate statistical methods.
• In clinical setup, study design are of mainly two types- Observational
study and Experimental study.
• Observational studies are hypothesis generating studies, and they can
be further divided into descriptive and analytic.
• Descriptive observational studies provide a description of the
exposure and/or the outcome.
• Analytic observational studies provide a measurement of the
association between the exposure and the outcome.

• Experimental studies, on the other hand, are hypothesis testing

studies. It involves an intervention that tests the association between
the exposure and outcome. Clinical trials come under experimental
studies.
 Strategies to eliminate errors and bias
1. Large sample size
2. Randomization
3. Blinding
4. Neutral observer
5. Use of calibrated equipment
 RCT and Non RCT
• Randomized Clinical Trials (RCTs) - In RCTs, trial participants are randomly
assigned to either treatment or control groups. The process of randomly
assigning a trial participant to treatment or control groups is called
“randomization”. Randomization removes potential for systematic error or
bias.
Types of randomization- simple, block and stratified
Simple randomization
• In simple randomization, the subjects are randomly allocated to
experiment/intervention groups based on a constant probability. This can be
performed in multiple ways, and one of which being as simple as a ‘flip of a
coin’ or using software.

Block randomization
• In block randomization, the subjects of similar characteristics are classified
into blocks. Then equal number of subjects from each group are randomly
assigned to the experiment/intervention group.

Stratified randomization
• In stratified randomization, the subjects are defined based on certain strata,
which are covariates. For example, prognostic factors like age can be
considered as a covariate, and then the specified population can be
randomized within each age group related to an experiment/intervention
group.
Blinding
• Blinding is a methodology adopted in a study design to intentionally not
provide information related to the allocation of the groups and test drug
to the subject participants, investigators and/or data analysts.
• Purpose- to decrease influence associated with the knowledge of being in
a particular group on the study result, and avoid bias from investigator or
data analyst.
• single-blinded study- the subject participants are not revealed which
group that they have been allocated to

• double-blinded studies- both the study participants and the investigator

will be unaware of the group to which they were allocated to.

• triple-blinded studies- the subject participants, investigators and data

analysts will not be aware of the group allocation.
Parallel group trial design
In parallel group randomisation, after randomisation each participant will stay in
their assigned treatment arm for the duration of the study. Parallel group design
can be applied to many diseases, allows running experiments simultaneously in a
number of groups, and groups can be in separate locations.
Cross-over trial design
Cross-over randomisation is when participants receive a sequence of different
treatments (for example, the candidate compound in the first phase and the
comparator/control in the second phase). Each treatment starts at an equivalent point,
and each individual serves as his/her own control. It presents some advantages, such as
low variance due to treatment and control being the same participant, and the
possibility of including a number of treatments. However, there must be a sufficient
time gap between the different treatment phases (washout period).
Non-randomised controlled clinical trial (Non-RCTs)
• A non-randomized clinical trial involves an approach to selecting controls
without randomization.
• With this type of study design a pattern is usually adopted, such as,
selection of subjects and controls from predefined pool with similar
characteristic.
• Depending on the approach adopted, the selection of subjects becomes
predictable and therefore, there is bias with regards to selection of
subjects and controls that would question the validity of the results
obtained.
Observational Study-
• Observational study originate to get the answer of – what, when, where, which, how.
• In clinical setup they are of following types-
Case reports and case series
Cohort
Case Control
Cross sectional

• Case reports and case series – These studies provide detailed and comprehensive
description of atypical or ‘out of the norm’ type of clinical presentation. It is one of the
earliest forms of research and provides an opportunity for the investigator to describe
the observations that make a case unique or describe a novel finding.
• A series of case reports make a case series which is an atypical presentation found in a
group of patients.
Cohort Study
• Cohort studies are study designs that compare two groups, such as the subjects
with exposure/risk factor to the subjects without exposure/risk factor, for
differences in incidence of outcome/disease.
• Most often, cohort study designs are used to study outcome(s) from a single
exposure/risk factor. Thus, cohort studies can also be hypothesis testing studies
and can infer and interpret a causal relationship between an exposure and a
proposed outcome, but cannot establish it.
• Prospective cohort studies- speculate the outcome of disease in future due to
exposure of certain factor.
• Retrospective cohort studies- identify a population with and without the risk
factor/exposure based on past records and then assess if they had developed the
disease/outcome at the time of study.
Case control study
• Case-control studies are study designs that compare two groups, such as
the subjects with disease (cases) to the subjects without disease
(controls), and to look for differences in risk factors.

• This study is used to study risk factors or etiologies for a disease, especially
if the disease is rare. Thus, case-control studies can also be hypothesis
testing studies and therefore can suggest a causal relationship but cannot
prove.

Cross sectional study

• Cross-sectional studies are study designs used to evaluate an association
between an exposure and outcome at the same time.
• These studies may be multicentric, involving large study population at
different location.