Name: Melo L.
Medecielo
Chapter Title: Drug Literature Evaluation II: Beyond the Randomized Controlled Trial
Definition of Terms:
1. Strengthening the Reporting of
Observational Studies in
Epidemiology - is a guidance
document that describes the
information that should be reported for
a cross sectional study, case control
study, or cohort study. Although
developed to assist authors and
reviewers/editors of journals, it can
also serve as a tool to help readers
identify important items for critical
appraisal.
2. Preferred Reporting Items for
Systematic Reviews and
Metaanalyses - is a guidance
document that describes the
information that should be reported for
a systematic review. Although
developed to assist authors and
reviewers/editors of journals, it can
also serve as a tool to help readers
identify important items for critical
appraisal.
3. Randomized controlled trial - is the
strongest study design for clinical
research, but several other designs,
such as observational studies and
reviews, are also commonly used.
4. Evidence based medicine - meaning
of EBM
5. Case report - it is a report
observations in a single patient or a
series of patients
6. Cross Sectional study - Identify
prevalence of characteristics of
diseases in populations
7. Case Control study - Determine
association between disease states
and previous exposure to risk factors
8. Cohort study - Determine association
between risk factors and subsequent
development of disease states
9. Narrative review - Summarize data
Summary
Studies that are observational, which typically
are used to find relationships between
variables outside of experimental trials that
entail a particular intervention on a
predetermined patient sample. They involve a
bigger population. Epidemiological studies
are typical instances of observational
research as establishing a link between
exposures and outcomes is something that
everyone is interested in. The first important
prospective observational research to be
carried out in the US was the Framingham
Heart Study, which started in 1948 and is now
in its third generation cohort. It has
significantly advanced our understanding of
cardiovascular disease risk factors and how
they influence the emergence of illness of the
heart. Notwithstanding the fact that these
cohorts might range from hundreds of
thousands of patients over decades.
Despite the limitations, observational studies
provide valuable information that may be
used in practice. These aren't blinded,
controlled studies. Observational research
can collect information about randomized
controlled trials that have a smaller sample
size, but epidemiological research, which are
vital for understanding more about public
health, have a much wider participant pool
concerning unusual side effects and the
security of drugs. One crucial consideration is
that observational studies can only connect
between exposures and results may be
inferred; only randomized controlled trials can
do cause and effect analysis trials. Yet,
observational studies can still offer a plethora
of information about the effectiveness of
drugs after they are approved, prescribed,
and used by the public.
Reviews of all types play a crucial role in the
literature of the biomedical sciences. Finding
a thorough overview of a certain topic is
 from multiple studies using possible with the help of narrative reviews.
nonsystematic, qualitative, and Systematic reviews are typically a necessary
subjective methods initial step in formulating guidelines, and they
10. Qualitative systematic review - are more important than a single research
Summarize data from multiple studies when it comes to rendering clinical judgments
using systematic, qualitative, and for patients. Despite the lack of a widely
objective methods accepted scale, systematic reviews or a large
11. Quantitative systematic review - body of high quality research with consistent
Summarize data from multiple studies findings are frequently viewed as having the
using systematic, quantitative, and highest degree of evidence. Because of this,
objective methods. it is essential for healthcare professionals to
12. N-of-trial - it compares effects of drug be able to critically evaluate them as their
to control during multiple observation prevalence increases.
periods in a single patient.
13. Health outcomes research - it Natural medicine use persists despite
compares outcomes and costs of drug variations in the ages or ethnicities that
therapies or services choose to take supplements and changes in
14. Stability study - Evaluate stability of the popularity of specific products. Like other
drugs in various preparations (e.g., medication suppliers, pharmacists must be
ophthalmologic, intravenous, topical, dependable and approachable sources of
and oral) information on alternative medicine. In public
15. Bioequivalence study - Assess places, supplements are sometimes placed
whether products are similar in rate next to the pharmacy with over-the-counter
and extent of absorption medications so that pharmacists are easily
16. Postmarketing study - Examine accessible for patient education and
efficacy and/or safety following customer inquiries. For the purpose of
approval of the drug by a regulatory making informed suggestions and
authority successfully guiding patients with natural
17. Quality improvement research - medicine inquiries, excellent natural medicine
Determine the impact and/or examination skills are essential.
economic value of systematic efforts
18. Survey research - Study the
prevalence, distribution, and
relationships of sociologic and
psychologic variables through use of
questionnaires applied to various
populations
19. Educational research - Investigate
aspects of education in order to
further knowledge
20. Observational studies - are used to
determine associations between
variables often involving a larger
population
21. Epidemiological studies - are
common examples of observational
studies, as there is an overall interest
in determining an association between
exposures and outcomes.
22. Institutional Review Board -
 meaning of IRB
23. Pantoprazole - a drug that leads to
the development of rhabdomyolysis
24. Barth syndrome - a rare autosomal
recessive condition appearing in
childhood that can result in
neutropenia, decreased growth, and
cardiomyopathy
25. Matching - process of creating two or
more groups of patients in
observational studies
26. Propensity scoring - is when each
patient having the risk factor or
exposure is assigned a score based
on all observed baseline
characteristics (e.g., sex, age,
weight); they are then matched
topatients without the risk factor or
exposure having a similar baseline
propensity score.
27. Confounder - is something other than
the independent variable that may
affect the outcome in an observational
study. Stratification - is when a
particular sample is divided into
subgroups based on characteristics
that might have an effect on outcomes
28. Sensitivity analysis - is a statistical
technique used to determine the
strength of a particular analysis of a
set of data by evaluating how results
are affected by changes in
methodology, unmeasured variables,
and/or general assumptions.
29. International Prospective Register
of Systematic Reviews - meaning of
PROSPERO
30. Aspirin - a drug that is a primary
prevention of cardiovascular disease
31. Funnel plot - is a scatterplot that
relates the estimate of effect size to
the weight of each individual study
32. Subgroup analysis - involves an
evaluation of the result in subsets of
the study sample (e.g., by gender,
race, geographic location), with tests
of interaction often used to determine
if between group differences are likely
to be due to chance.
33. Sensitivity analysis -is an
 assessment of the result under
different conditions (e.g., using a
different method of pooling data,
removing low quality studies,
excluding an unusually large study
34. Meta Regression analysis - , is a
statistical technique to evaluate the
influence of certain covariates (e.g.,
drug dose, patient age, treatment
duration) on the result and is typically
reported as slope coefficients with
CIs.
35. Health outcomes research - is
defined as the effect clinicians and
health care organizations have on
improving patients’ health
36. Agency for Healthcare Research
and Quality - meaning of AHRQ
37. Patient-Centered Outcomes
Research Institute - meaning of
PCORI
38. Stability studies - establish the
quality of an active pharmaceutical
ingredient (API) or finished
pharmaceutical product (FPP) when
exposed to various environmental
factors like temperature, light, and
humidity
39. Bioequivalence studies - are
designed to show that the generic
product has the same quality, safety,
and efficacy of the reference product
40. Phase IV studies - are designed to
further research on a medication after
approval by a regulating agency.
41. Efficacy - is determined how well the
medication works under ideal
conditions.
42. Survey research - is the
methodological collection of
information from respondents
including facts, opinions, knowledge,
mindsets, and behavior
43. Educational research - has been
defined as the “systematic and critical
investigation of education that
advances knowledge and benefits
society by allowing people to live fuller
lives
44. Quantitative research - uses
 numbers and mathematics to define
relationships, describe populations,
and test hypotheses.
45. Qualitative research - uses
descriptive, nonnumerical data from
surveys, focus groups, and
documents to comprehend a specific
population.
46. Sampling error - is when, by chance,
the sample taken does not accurately
represent all possible subjects of the
population of interest. Using diverse
recruitment strategies and large
sample sizes can reduce the
possibility of sampling error.
47. Measurement error - is a problem
with how data are collected, either
because questions do not coincide
with the topic of interest or do not
induce truthful answers from
participants

Self-Assessment questions
Copy + Paste the Self-Assessment questions. Provide your answer and rationale with
citations. Follow the sample given below.

Answer:
Choice: A
Rationale:

1. Which listing of observational designs is in the correct order for the studies described
above?
a. Cohort, case­control, cross­sectional
b. Cross­sectional, case­control, cohort
c. Case­control, cohort, case series
d. Cohort, cross­sectional, case­control
Answer : Cohort, Case-control, cross-sectional
Choice : A.
Rationale : The correct order of observational designs on the case study are Cohort,
Case-control, cross-sectional. They can be used to distinguish between cause and effect
since they measure occurrences in chronological sequence. Prevalence is determined
using cross-sectional studies. They are quick and simple, but they do not allow for the
separation of cause and effect. Case controlled studies compare groups in the past. They
are valuable for examining rare diseases or outcomes because they strive to discover
potential determinants of outcome. They are frequently used to create hypotheses, which
are then tested in prospective cohort other research.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 2

2. Which ranking of observational study designs is in order of decreasing rigor?

a. Retrospective cohort > case series > case­control
b. Cross­sectional > case­control > retrospective cohort
c. Case­control > case report > prospective cohort
d. Prospective cohort > case­control > case series

nswer: Prospective cohort> case-control > case series

Choice : D.
Rationale : In terms of statistical analysis, which is commonly found at the end of the
methodology section just before the results, the three most common and important tests
used in observational studies are the relative risk (RR), odds ratio (OR), and hazard ratio
(HR).1,34 RR is also called the true risk and is used for prospective cohort studies. Case
Control studies are a step above cross sectional studies in terms of level of evidence and
study rigor, as more patients can be involved through the use of electronic medical records
and large databases. Subsequently, more significant associations can be determined from
the results due to the increased numbers of subjects, and because medical records and
previously established databases are more dependable than surveys, observations may be
considered more reliable. A case series is a description of a clinical observation in a single
patient, and a case series is a description of a clinical observation in a small group of
patients.2 Most would consider these to be the weakest type of evidence relating to EBM
practices and research.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 5-11

3. Which observational study design involves a control group and retrospective data
collection?
a. Case series
b. Cross­sectional
c. Case­control
d. Prospective cohort

Answer : Case-Control
Choice : C.
Rationale : Case Control studies are a step above cross sectional studies in terms of level
of evidence and study rigor, as more patients can be involved through the use of electronic
medical records and large databases. Subsequently, more significant associations can be
determined from the results due to the increased numbers of subjects, and because
medical records and previously established databases are more dependable than surveys,
observations may be considered more reliable. These types of studies examine a particular
outcome of interest (e.g., adverse effect of a drug, disease/condition) and then go back in
time (i.e., retrospective) to determine risk factors or exposures to what may have caused
the particular outcome.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 6

4. Which technique is used to produce groups that are similar at baseline in observational
studies?
a. Adjustment of odds ratios
b. Propensity score matching
c. Randomization
d. Sensitivity analyses

Answer : Propensity score matching

Choice : B.
Rationale : Propensity scoring is when each patient having the risk factor or exposure is
assigned a score based on all observed baseline characteristics (e.g., sex, age, weight);
they are then matched to patients without the risk factor or exposure having a similar
baseline propensity score. This is different from matching cases and controls based on one
or two characteristics, as the propensity score takes into account all traits. By observing all
baseline characteristics through propensity scoring, this often leads to fewer statistically
significant differences. In observational studies, matched propensity scoring between
samples also allows investigators to have a more precise estimation of treatment response,
approaching that of randomized controlled trials, by more closely matching groups based
on these scores.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 10

5. Which of the following is a confounding variable in an observational study to evaluate

whether medications used to treat attention-deficit/hyperactivity disorder are associated
with cardiovascular events?
a. Methylphenidate
b. Myocardial infarction
c. Smoking
d. Sudden cardiac death

Answer : Smoking
Choice : C.
Rationale : In general, a sample of the population is chosen without a particular disease or
condition (e.g., chronic obstructive pulmonary disease).1,2 Investigators usually start by
evaluating one risk factor or exposure (e.g., smoking, environmental toxin) hypothesized to
contribute to the disease and follow those patients over time to determine whether or not
the disease occurs.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 7

6. Which characteristic is unique to quantitative systematic reviews?

a. Focused clinical question
b. Comprehensive literature search
c. Specific inclusion and exclusion criteria
d. Method for pooling data

Answer : Method for pooling data

Choice : D.
Rationale : The model for pooling data is another unique consideration for quantitative
systematic reviews.41,51 Typically, data are combined statistically using a fixedeffect model
or a random effects model, which should be stated by the authors in the methods section.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 22

7. What does the Cochrane risk­of­bias tool assess in a systematic review?

a. Likelihood of publication bias
b. Quality of individual studies that are included
c. Statistical significance of the results for the main analysis
d. Consistency among reviewers in determining if studies meet the eligibility criteria

Answer : Quality of individual studies that are included

Choice : B.
Rationale : A process for assessing the quality (i.e., risk of bias) of the individual studies
that are included in a systematic review is important.39,41,51 Numerous scales and
checklists exist for this purpose, but many are associated with significant limitations (e.g.,
rating a study as low quality due to lack of blinding, even if blinding was not possible). To
overcome those limitations, the Cochrane risk of bias tool was developed and is
recommended for systematic reviews of randomized controlled trials (systematic reviews of
observational studies would require a different instrument).50,51,60 It typically involves
questions in six domains (randomization, allocation concealment, blinding, incomplete
outcome data, selective outcome reporting, and other) to assess five types of bias
(selection, performance, attrition, detection, and reporting) for each study.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 23

8. In a meta­analysis on feverfew for migraines, the p value for heterogeneity was 0.00001
and the I2 value was 72% for the pooled analysis of the

primary outcome. Which of the following is an accurate interpretation of the heterogeneity?

a. Low in extent
b. Not assessed adequately
c. Not statistically significant
d. Undesirable

Answer : Undesirable
Choice : D.
Rationale : Undesirable. Since the supporting or quality evidence is lacking.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 17

9. In a meta­analysis on medications to treat alcohol dependence, the pooled result using a

random­effects model for the primary outcome of return
to drinking was RR 0.89 (95% CI, 0.67–0.99). Which trial would have carried the most
weight in the analysis?
a. N=25; RR 1.08 (95% CI, 0.91–1.27)
b. N=68; RR 0.85 (95% CI, 0.79–0.99)
c. N=104; RR 0.94 (95% CI, 0.87–1.01)
d. N=212; RR 0.58 (95% CI, 0.31–1.10)

Answer : N=104; RR 0.94 (95% Cl, 0.87-1.01)

Choice : C
Rationale : The relative risk and confidence interval is higher with 0.94 and 0.87-1.01 which
means it have the most weight carried in the analysis.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 11

10. Which results are desirable for publication bias evaluated with a funnel plot in a
quantitative systematic review?
a. Symmetry; p = 0.65
b. Symmetry; p = 0.04
c. Asymmetry; p = 0.01
d. Asymmetry; p = 0.15

Answer : Symmetry; p = 0.65

Choice : A.
Rationale : Symmetry in an inverted funnel indicates that studies with smaller and larger
effects than the pooled effect were included in the metaanalysis and quantitative systematic
review, which is the desirable result and suggests that publication bias is unlikely.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 23

11. Which type of study is typically conducted after a medication has been approved and is
necessary to meet regulatory requirements?
a. Stability
b. Bioequivalence
c. Postmarketing
d. Quality improvement

Answer : Postmarketing
Choice : C
Rationale : Postmarketing, Examine efficacy and/or safety following approval of the drug by
a regulatory authority.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 3

12. Which type of research is affiliated with a specific study design?

a. N­of­1
b. Health outcomes
c. Quality improvement
d. Educational

Answer : N-of-1
Choice : A.
Rationale : N-of-1 trials are controlled trials that often use gold standard techniques,
including randomization, blinding, and specific study design conducted in a single patient in
order to evaluate treatment effectiveness. Because results from randomized controlled trials
cannot predict effect in any one person, Nof1 trials are useful to clinicians and patients,
particularly for rare disease states, comorbid conditions, and patients using concurrent
therapies. Because both study types involve a single patient, Nof1 trials might be confused
with case reports, but these two studies differ in several ways , including that Nof1 trials are
controlled through repeated testing of the individual patient with both intervention and
control, whereas case reports describe a single observation with no comparator.
Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 26

13. Which element is essential in survey research?

a. Systematic questionnaire
b. Convenient population of interest
c. Simple recruitment strategy
d. Well­intentioned research question

Answer : Systematic Questionnaire

Choice : A.
Rationale : Systematic questionnaire , which may also be described as a metaanalysis, is a
summary of previously conducted studies that uses specific criteria to address a question
and statistically combines the data.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 17

14. Which characteristic is important to identify in a botanical natural medicine study?

a. Duration, because these studies are often long
b. Number of participants, because these studies are often large
c. Legal status, because the FDA must approve plant­derived medicines
d. Standardization, because plant­derived products often contain many different chemical
entities

Answer : Standardization, because plant-derived products often contain many different

chemical entities
Choice : D.
Rationale : Standardization have principles and criteria used to analyze the quality of drug
literature are used to analyze natural medicines medical literature.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 2

15. Your hospital is considering a request to allow the use of powdered ginger root capsules
for prevention and treatment of postoperative nausea and
vomiting. Which literature would be appropriate to include in your analysis to make a final
decision?
a. Two retrospective analyses of powdered ginger root capsules in 3845 women for
prevention of pregnancy­associated nausea and vomiting
b. A randomized, single­blind, placebo­controlled trial of powdered ginger root capsules in 80
patients with previous severe postoperative nausea
and vomiting
c. A randomized, double­blind, placebo­controlled trial of dried standardized ginger leaf
extract in 372 patients with previous moderate
postoperative nausea and vomiting
d. Two randomized controlled trials of ginger root extract added to standard antiemetic
therapy in 423 patients receiving chemotherapy for
gynecological malignancies

Answer : A randomized, single-blind, placebo-controlled trial of powdered ginger root

capsules in 80 patients with previous severe postoperative nausea and vomiting
Choice : B.
Rationale : The randomized controlled trial is the strongest study design for clinical
research, but several other designs, such as observational studies and reviews, are also
commonly used. Each study design is useful for specific situations, has inherent strengths
and weaknesses, and involves some unique methodologies. Because all relevant literature
should be considered when practicing evidence based medicine (EBM), it is vital to
understand how to evaluate all study designs. The purpose of this chapter is to familiarize
the health care practitioner with the uses, strengths, weaknesses, and unique
methodologies for study designs beyond the randomized controlled trial.

Reference:
Haber, S., Cooper, J., Wisniewski, C., McQueen, C. (2023). Drug Information: A
Guide for Pharmacists. 2

References (APA 7th ed)