4. Introduction
To graduate students and researchers unfamiliar with case study methodology, there is
often misunderstanding about what a case study is and how it, as a form of qualitative
research.
Case study is a form of qualitative descriptive research that is used to look at
individuals, a small group of participants, or a group as a whole. This qualitative
method of study emphasizes detailed contextual analysis of a limited number of events
or conditions and their relationships. Researchers have used the case study research
method for many years across a variety of disciplines.
5. Case Study – Defined
• It is a systematic inquiry into an event or a set of related events which aims to
describe and explain the phenomenon of interest.
• It refers to the collection and presentation of detailed information about a
particular participant or small group, frequently including the accounts of subjects
themselves.
• It is an in depth study of a particular situation rather than a sweeping statistical
survey.
6. • Through case study, a researcher can closely examine the data within a specific context.
• Through case study, a researcher can examine contemporary real-life situations and
provide the basis for the application of ideas and extension of methods.
• Through case study, a researcher can test theoretical models by using them in real world
situations.
• A case study may not answer a question completely, but it will give some indications and
allow further elaboration and hypothesis creation on a subject.
7. Why use a case study?
• Case studies are a great way to improve a learning experience, because they get the
learner involved, and encourage immediate use of newly acquired skills.
• They differ from lectures or assigned readings, because they they require participation and
deliberate application of a broad range of skills.
• Case studies help researchers make the difference between knowing what to do. And
knowing how, when, and why to do it.
8. Case Study Applications
• Utilization of the case study as a teaching method. Practical application and testing of
scholarly knowledge.
• Provides an approximation of various professional environments (i.e. classroom, board
courtroom, or hospital).
• Incorporates the idea that students can learn from one another "by engaging with each
other and with each other's ideas, by asserting something and then having it
questioned, challenged and thrown back at them so that they can reflect on what they
hear, and then refine what they say".
9. Designs of Case Study
• To obtain as complete a picture of the participant as possible, case study researchers
can employ a variety of a variety of case study designs. Some common designs include
single-case and multiple-case design.
• Single-case design - It is where events are limited to a single occurrence. However,
the drawback of this design is its inability to provide a generalizing conclusion, in
particular when the events are rare.
• Multiple-case design - It can be adopted with real-life events that show numerous
sources of evidence through replication rather than sampling logic.
10. Types of Case Study
1. Explanatory - This type of case study would be used if you were seeking to answer a
question that sought to explain the presumed causal links in real-life interventions
that are too complex for the survey or experimental strategies.
Example: Joia (2002). Analysing a web-based e-commerce learning community: A case
study in Brazil. Internet Research, 12, 305-317.
2. Exploratory - It is a type of case study that is used to explore those situations in which
the intervention being evaluated has no clear, single set of outcomes.
Example: Lotzkar & Bottorff (2001). An observational study of the development of a
nurse-patient relationship. Clinical Nursing Research, 10, 275-294
11. 3. Descriptive - This type of case study is used to describe an intervention or phenomenon
and the real-life context in which it occurred.
Example: Tolson, Fleming, & Schartau (2002). Coping with menstruation: Understanding
the needs of women with Parkinson's disease. Journal of Advanced Nursing, 40, 513- 521.
4. Multiple Case Study - It enables the researcher to explore differences within and
between cases.
Example: Campbell & Ahrens (1998). Innovative community services for rape victims: An
application of multiple case study methodology. American Journal of Community
Psychology, 26, 537-571.
12. 5. Intrinsic-The term 'intrinsic' suggests that researchers who have a genuine interest in
the case should use this approach when the intent is to better understand the case. It is not
undertaken primarily because the case represents other cases or because it illustrates a
particular trait or problem, but because in all its particularity and ordinariness, the case
itself is of interest
• .Example: Hellström, Nolan, & Lundh (2005). "We do things together" A case study of
"couplehood" in dementia. Dementia, 4 (1), 7-22.
6. Instrumental - It is used to accomplish something other than understanding a
particular situation. It provides insight into an issue or helps to refine a theory.
Example: Luck, Jackson, & Usher (2007). STAMP: Components of observable
behaviour that indicate potential for patient violence in emergency departments.
13. 7. Collective - It is similar in nature and description to multiple case studies.
Example: Scheib (2003). Role stress in the professional life of the school music teacher: A
collective case study. Journal of Research in Music Education, 51,124-136
14. Advantages and Limitations of Case Study
• The primary advantage of case study is that it provides much more detailed information
than what is available through other methods, such as surveys. Case studies also allow
one to present data collected from multiple methods.
• Can be lengthy- Because they provide detailed information about the case in narrative
form, it may be difficult to hold a reader's interest if too lengthy.
• Concern that case studies lack rigor- Case studies have been viewed in the evaluation
and research fields as less rigorous than surveys or other methods. Reasons for this
include the fact that qualitative research in general is still considered unscientific by
some and in many cases, case study researchers have not been systematic in their data
collection or have allowed bias in their findings.
15. Steps Involved in a Case Study
The steps involved in a case study are as follows:
1. Plan
• Identify stakeholders who will be involved.
• Brainstorm a case study topic, considering types of cases and why they are unique or
of interest.
• Identify what information is needed and from whom
• Identify any documents needed for review.
• List stakeholders to be interviewed or surveyed (national, facility, and beneficiary
levels) and determine sample if necessary.
• Ensure research will follow international and national ethical research standards,
including review by ethical research committees.
16. 2. Develop Instruments
• Develop interview/survey protocols the rules that guide the administration and
implementation of the interview/survey. Put simply, these are the instructions that are
followed to ensure consistency across interviews/surveys, and thus increase the
reliability of the findings.
• Develop an interview guide/survey that lists the questions or issues to be explored and
includes an informed consent form. Please note that you will likely 16 need interview
guides/surveys for each group of stakeholders, as questions may differ.
• Where necessary, translate guides into local languages and test translation.
17. 3. Train Data Collectors.
• Identify and train data collectors (if necessary).
4. Collect Data
• Gather all relevant documents.
• Set up interviews/surveys with stakeholders.
• Seek informed consent of each respondent (written or documented oral).If the respondent
has consented,interview/survey.
18. 5. Analyze Data
• Review all relevant documents.
• Review all interview/survey data.
6. Disseminate Findings
• Write report.
• Solicit feedback.
• Revise Disseminate.
20. Introduction
• A carbon atom to which four different groups are attached is chiral.
• Enantiomers are chiral molecules that are mirror images of one another. Furthermore, the
molecules are non-superimposable on one another. This means that the molecules cannot be
placed on top of one another and give the same molecule.
21. • Enantiomers differ in the direction that they rotate plane polarized light.
• S(sinister)-enantiomer = anticlockwise
• R(rectus)-enantiomer = clockwise
22. • Molecules having more than one asymmetric centre but which are not mirror images of
each other are termed diastereoisomers and are physically different.
• Solutions of enantiomers rotate polarized light. An enantiomer which rotates light to the
right is dextrorotatory, abbreviated as d or (+).
• The other enantiomer will rotate the light to the left by the same absolute magnitude
and is levorotatory, abbreviated as l or (-).
• A racemate is an equal mixture of the enantiomers and does not rotate polarized light.
23. • The enantiomers of a chiral drug differ in their interactions with enzymes, proteins,
receptors and other chiral molecules to including chiral catalysts.
• These differences in interactions, in turn, lead to differences in the biological activities
of the two enantiomers, such as their pharmacology, pharmacokinetics, metabolism,
toxicity, immune response etc.
• *Surprisingly, biological systems can recognize the two enantiomers as two very
different substances.
24. • Easson-Stedman's illustration of hypothetical interaction between the two enantiomers
of a racemic drug with a receptor at the drug binding sites: The three substituents A, B,
C of the active enantiomer (left) can interact with three binding sites a, b, c of a
receptor by forming three contacts Aa, Bb and Cc. whereas the inactive enantiomer
(right) cannot because the contact is insufficient.
25.
26. Pharmacokinetics stereoselectivty
• Absorption.
Passive intestinal absorption
Carrier transporter stereoselectivity
• Distribution
Protein binding
Tissue distribution
• Metabolism
first pass metabolism
Phase I and phase II metabolism
• Elimination
27. Absorption and stereoselectivity
• Passive intestinal absorption: For majority of racemic drugs, absorption appears to be
by passive diffusion, provided no stereoselectivity
28. • Carrier mediated transporter: Stereo selective intestinal transporter is the main
cause for marked difference in the oral absorption of enantiomers.
• L-Methotrexate have 40 fold higher Cmax and AUC than D- Methotrexate
29.
30. • There was a 15% difference in the bioavailability of the enantiomers of atenolol,
Although it was postulated that this was a enantioselective active absorption results.
• Pharmacokinetic differences resulting out of stereoisomerism can be in absorption like
L- Methotrexate is better absorbed than D- Methotrexate.
• Esomeprazole is more bioavailable than racemic omeprazole.
31. • Although levodopa(L-dopa) is absorbed much more rapidly than D-dopa, they are both
absorbed to the same extent.
32. DISTRIBUTION
• Stereo selectivity in drug distribution may occur as a result of binding to either plasma
or tissue proteins and transport via specific tissue uptake and storage mechanisms
• The majority of drugs bind in a reversible manner to plasma proteins, notably to human
serum albumin (HSA) and/or α-acid glycoprotein(AGP).
• Acidic drugs bind preferentially to HSA and basic drugs predominantely bind to AGP.
33. Protein binding
• Stereoselective plasma protein binding could influence distribution and elimination
because the major determinant of drug distribution and elimination is protein binding.
34. • The free fraction of R-enantiomer of propranolol is greater than that of S-enantiomer of
propranolol.
• The enantiomers may display different magnitudes of stereoselectivity between the
various proteins found in plasma the R-propranolol binding to albumin is greater than S-
propranolol. The opposite is observed for α - acid glycoprotein.
• S-Warfarin is more extensively bound to albumin than R-Warfarin, hence it has lower
volume of distribution.
35.
36. • Levocetrizine has smaller volume of distribution than its dextroisomer.
• There is enantio selective protein binding interaction reported b/w warfarin & lorazepam
acetate.
• R,S-warfarin allosterically increased the binding of S- lorazepam acetate, but there was no
effect on them R-enantiomer.
• Similarly, S-lorazepam acetate increased the binding of R,S-warfarin.
37. • Enantio selective tissue uptake, which is in part a consequence of enantio selective
plasma protein binding, has been reported
For example, the transport of ibuprofen into both synovial and blister fluids is
preferential for the S- enantiomer owing to the higher free fraction of this enantiomer
in plasma.
• In addition, the affinity of stereoisomers for binding sites in specific tissues may also
differ and contribute to stereo selective tissue binding
Eg:- S-leucovorin accumulates in tumor cell invitro to a greater degree than the R
enantiomer
38. METABOLISM
• stereoselectivity in metabolism is probably responsible for the majority of the
differences a observed in enantioselective drug disposition.
• Stereoselectivity in metabolism may arise from differences in the binding of
enantiomeric substrates to the enzyme active site and/or be associated with catalysis
owing to differential reactivity and orientation of the target groups to the catalytic site.
• As a result, pair of enantiomers is frequently metabolized at different rates and/or via
different routes to yield alternative products.
39.
40. • The stereoselectivity of the reactions of drug metabolism may be classified into three
groups in terms of their selectivity with respect to the substrate, the product, or both.
• substrate selectivity - one enantiomer is metabolized more rapidly than the other.
• product stereoselectivity - in which one particular stereoisomer of a metabolite is
produced preferentially
• substrate- product stereoselectivity - where one enantiomer is preferentially
metabolized to yield a particular diastereoisomeric product
41. • Using this approach, metabolic pathways maybe divided into five groups.
• Prochiral to chiral transformations
• Chiral to chiral transformations
• Chiral to diastereoisomer transformations
• Chiral to achiral transformations
• Chiral inversion
42. Prochiral to chiral transformations
• Metabolism taking place either at a prochiral center or on an enantiotopic group within
the molecule.
1. For example, The prochiral sulphide cimetidine undergoes sulphoxidation to yield
the corresponding sulphoxide, the enantiomeric composition.
43. 2. Phenytoin undergoes Stereoselective para- hydroxylation to yield (S)-4'-
hydroxyphenytoin, which is greater i.e. 90% than other enantiomer.
44. • Chiral to chiral transformations
• The individual enantiomers of a drug undergo metabolism at a site remote from the
centre of chirality with no configurational consequences.
• For example(S)-warfarin undergoes aromatic oxidation mediated by CYP 2C9 in the 7-
and 6-positions to yield (S)-7-hydroxy- and (S)-6- hydroxywarfarin in the ratio 3.5: 1.
45. • Chiral to diastereoisomer transformations
• A second chiral centre is introduced into the drug either by reaction at a prochiral centre
or via conjugation with a chiral conjugating agent.
• Eg- aliphatic oxidation of pentobarbitone and the keto- reduction of warfarin to yield the
corresponding diastereoisomeric alcohol derivatives or the stereoselective
glucuronidation of oxazepam.
46. • Chiral to achiral transformations:
• The substrate undergoes metabolism at the center of chirality, resulting in a loss of
asymmetry.
Examples :Aromatization of the dihydropyridine calcium channel blocking agents, e.g.,
Nilvadipine, to yield the corresponding pyridine derivative.
47. Examples
• Omperazole, which undergoes CYP 3A4-mediated oxidation at the chiral sulphoxide to yield
the corresponding sulphone.
• the reaction shows tenfold selectivity for the S-enantiomer in terms of intrinsic clearance.
48. • Chiral inversion:
• one stereoisomer is metabolically converted into its enantiomer with no other alteration
in structure.
• Agents undergoing this type of transformations
✓ 2-aryl propionic acid (2-APAs)
✓NSAIDS (eg;ibuprofen, fenoprofen, flurbiprofen,ketoprofen)
✓ 2-aryloxypropionic acid herbicide (eg:haloxyfop)
• In the case of the 2-APAS, the reaction is essentially stereospecific, the less active, or
inactive, R- enantiomers undergoing inversion to the active S- enantiomers.
49. RENAL EXCRETION
• Stereo selectivity in renal clearance may arise as a result of either selectivity in protein
binding, influencing glomerular filtration and passive reabsorption, or active secretion
or reabsorption.
• Enantio selectivity in renal clearance with enantiomeric ratios between 1.0 and 3.0 In
the case of the diastereoisomers quinine and quinidine-clearance is about 24.7 and 99
mLmin-1 respectively.
50. • For those agents that undergo active tubular secretion, interactions between
enantiomers may occur such that their excretion differs following administration as
single enantiomers versus the racemat.
EXAMPLE:-
• 1 Administration of the quinolone antimicrobial agent (S)- ofloxacin with increasing
amounts of the R-enantiomer to the cynomolgus monkey which results in a reduction in
both the total and the renal clearance of the S-enantiomer.
• MECHANISM:-By competitive inhibition of transport mechanism (organic cation
transport system)
51. Case Study 1.
• Wade et al reported that the absorption of dopa from rat small intestine was an active
process which favoured the L-enantiomer.
• It was later noted that D-dopa is also absorbed, but by passive diffusion. The active
absorption of methotrexate also favors the L-enantiomer.
• Chiral B-lactam antibiotics are actively absorbed via the dipeptide transport system
which is present in the intestinal brush border membrane.
52. Case Study 2:
• The (+) enantiomer of propranolol is largely devoid of B-blocking activity.The study on
propranolol, has been found to show effective an anti-fertility action.
• When used topically in combination with nonoxynol-9 sperm motility was significantly
reduced as compare to use of nonoxynol-9 alone.
• The basis of the effect was thought to be due to membrane stabilizing effect of
propranolol which is shared between two enantiomers.