Research Designs

CRUZ, CHARLIEMAIGN STANLEY
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RESEARCH DESIGNS
Although the randomized controlled trial is

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the most frequently used study design for

clinical research, several other designs are
used in specific situations, such as
investigating rare outcome incidences,
studying equivalency/noninferiority between
drugs, or minimizing patient exposure to new
drugs with inadequate efficacy.
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Variations of Controlled Clinical Trial

1. Non-inferiority Trial
2. N-of-1 Trial
3. Adaptive Clinical Trial
4. Stability Studies/In Vitro Studies
5. Bioequivalence Trials
6. Programmatic Research
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NON-INFERIORITY (NI) TRIALS

● seek to show that any difference between two
treatments is small enough to conclude the test
drug has "an effect not too much smaller than
the active control" or reference drug
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NON-INFERIORITY (NI) TRIALS

Other randomized, controlled, clinical trials to determine
outcomes between comparative drugs
● Superiority trials - the aim is to determine that one drug is

superior to the other
● Equivalency trials - designed to determine if the new drug is
therapeutically similar to the control drug
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NI TRIALS
● is often considered when superiority of a test drug over a
reference drug (for instance standard of care) is not
anticipated
○ the objective is showing the test drug to be statistically
and clinically not inferior to the reference drug
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NI TRIALS
● considered when the use of a superiority trial would be
considered unethical
○ Superiority trial of Drug A vs. placebo
○ it is unethical to use a placebo when there is available
effective treatment that possesses an important benefit
such as preventing death or irreversible injury to the
patient
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NI TRIALS - DESIGN
● focuses on the mean difference in efficacy measures between
the test drug versus reference drug
● NI margin - can show how much better the reference drug's
effect can be and still allow the test drug to be considered
non-inferior
○ correctly determining this margin is considered the
greatest challenge in the design and interpretation of NI
trials
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NI TRIALS - STATISTICAL RATIONALE

● the defining parameters for the null and alternative
hypotheses differ from those used with superiority trials
● null hypothesis - reference drug is significantly different
from the test drug by at least the established NI margin
● alternative hypothesis - reference drug is not significantly
different from the test drug by not exceeding the established
NI margin
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Check also for:
● Assay Sensitivity - the reference drug being used must have

an established effect over placebo in order to further
conclude the possible observed efficacy of a test drug when
compared to the reference drug.
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Check also for:
● Constancy Assumption - important parameters from

previously conducted studies must be made identical to
ensure the effectiveness of the reference and test drug being
observed in the present.
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N-of-1 Trial
● attempts to apply the principles of clinical trials, such as
randomization and blinding, to individual patients
● useful when the beneficial effects of a particular treatment in
an individual patient are in doubt
● advantageous if the treatment has a short half-life (allowing
multiple crossover periods without carryover effects) and is
being used for symptomatic relief of a chronic condition
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N-of-1 Trial
● attempts to apply the principles of clinical trials, such as
randomization and blinding, to individual patients
● useful when the beneficial effects of a particular treatment in
an individual patient are in doubt
● advantageous if the treatment has a short half-life (allowing
multiple crossover periods without carryover effects) and is
being used for symptomatic relief of a chronic condition
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N-of-1 Trial Case Study
Retrospective
Design Prospective
(most often)
Predefined methods Yes No
Clearly defined outcome
Yes No
measures
Randomization Yes No
Blinding Yes No
Multiple treatment
Yes Not usually
periods
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ADAPTIVE CLINICAL TRIALS

● provides enough flexibility to incorporate continuously emerging knowledge
generated as a trial is carried out
● provides an opportunity to change some study methodology when they identify
things that may need to be done differently
○ different dose, different patients, or measuring different outcomes over a different period of time
● staged protocol or group sequential trial
○ 3+3 trial - three patients start at a specific dose, and if no toxicity is noted, a second group of three
patients are given a higher dose
● fewer patients are allocated to a less-effective therapy
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Stability Studies/In Vitro Studies

● determine the stability of drugs in various preparations (e.g., ophthalmologic,
intravenous, topical, and oral) under various conditions
● knowing the length of time a particular preparation is stable
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Bioequivalence Trials
● establish that the quality, safety, and efficacy of generic drugs are the same as the
brand name product
● FDA regulations require that bioequivalence between the generic product and the
brand name product be demonstrated
● conducted under standardized conditions in normal healthy adult volunteers
Bioequivalent products - products that are equivalent in rate and extent of absorption
● in a bioequivalence trial, a 10% difference between products would be equivalent,

whereas, a 10% difference between the products in a superiority trial could easily
be deemed as meaning that there is a difference
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Programmatic Research
● focused on the impact and economic value of programs and services provided by
pharmacists in community and institutional settings
○ limited resources and budget constraints demand that only those services that improve patient care
in a cost-effective manner should be implemented
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Observational Study Design

● used in specific situations such as when large populations of patients must be
followed over extended periods of time
● can be prospective, retrospective, or a single snapshot (or slice) in time
● interpretation of results from these types of trials only allows associations to be
formed, rather than true cause-and-effect relationships
1. Cohort Studies
2. Case-control Studies
3. Cross-sectional Studies
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Exposure Outcome Study Study
Prospective Retrospective
Observational Known at Known at Determines Determines
Data Data
Study Design Beginning Beginning of Exposure Outcome
Collection Collection
of Study Study Status Occurrence
Cohort X X X
Case-control
X X X
(trohoc)
Cross-sectional X X X
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Cohort Studies
● Cohort - describe a group of individuals with a common characteristic or
experience
○ a specific exposure to a particular agent such as a vaccine, medication, procedure, or
environmental toxin
● follow-up, incidence, and longitudinal studies
● participants are grouped by their exposure and followed over time to determine
the incidence of symptoms, disease, or death
● Two groups are usually compared
○ exposed
○ non-exposed
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Cohort Studies
Categories:
1. prospective (looking forward in time)/concurrent

● participants are monitored over time, groups the participants based on
current or past exposure and then follows these groups over time, observing
the various predetermined outcomes
2. retrospective(looking back in time)/historical/nonconcurrent
● both the exposure and the outcome are already recorded in a database, uses
computerized data on patients that has been recorded over the natural course
of their health care
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Cohort Studies
Categories:
3. ambidirectional (looking both forward and backward in time)

● involves both prospective and retrospective components
● Ex. Air Force Health Study looking at pilots involved in aerial spraying of
herbicides including Agent Orange during the Vietnam War. The
retrospective portion of the study observed the incidence of cancer and
mortality from time of exposure in the war through the 1980s while the
prospective component involves observing these men well into the future
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Cohort Studies
Other terms describing cohort studies:
1. open or dynamic - participants may enter or leave based on changing

characteristics, such as smoking, alcohol consumption, occupation, specific
geographical location
2. fixed - identified by an unchangeable event such as having undergone a surgical
procedure or been exposed to a potential toxin like Agent Orange at a specific
time
○ exposures do not change or are considered fixed
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Cohort Studies
Other terms describing cohort studies:
3. closed - involves an unchangeable event

○ has a specific starting and ending point that involves follow-up
○ participants attending a high school football game to determine if the nachos and spicy cheese
consumed at the game provided them discomfort such as gastritis throughout the remainder of the
evening until morning
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Cohort Studies
● used to investigate the cause of a disease or the benefits and safety risks of both
medication and procedures
● simplest approach for studying disease incidence
● disadvantages - expense and time consumption
● attempts to establish a relationship between an exposure or risk factor and a
subsequent outcome - relative risk
○ risk of developing a disease or adverse event in those participants exposed to a specific variable
compared to those not exposed to that variable
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Cohort Studies
● no randomization process that occurs to ensure that each participant has an equal
opportunity to be in either the exposed or non-exposed group
● a cohort study has no assurance of this similarity
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Cohort Studies
● two concerns arise:
○ selection bias - is a potential whenever the investigator is allowed to decide who is
brought into the study and who is not selected to participate
■ an investigator either knowingly or unknowingly selects from the general
population only the healthiest individuals to be assigned to the non-exposure
group while at the same time a mixture of healthy and unhealthy participants are
selected for the exposure group
○ confounder - is a variable related to one or more variables defined in the study
■ is common since they are the product of not using a randomization schedule
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Cohort Studies
● accurate measurement of the outcome is essential
○ surveillance bias is a potential problem when one group, generally the
exposed group is more intensely monitored for changes in the outcome
measure than the comparison group
■ blinding the investigator to reduce bias
○ information bias can occur if the same efforts to measure outcomes are not
made for both the exposed and non-exposed groups
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Case-Controlled Studies
● case-referent / case history / retrospective studies /trohoc
studies
● seek to retrospectively identify potential risk factors of
diseases or outcomes
● subjects (cases) with a particular characteristic or outcome of
interest (e.g., disease) are recruited, matched with, and
compared to a similar group of subjects (controls) who have
not experienced the characteristic or outcome
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● data are collected retrospectively via patient interviews or by
reviewing subject data records, and the two groups are
compared to identify possible risk factors or contributors for
development of the disease or outcome of interest
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● more useful when diseases have a rare prevalence or when
many years of exposure to the risk factor is required
● predisposition to the disease of interest should be similar in
both cases and controls, except for exposure to the risk factor
under investigation; however, this is extremely difficult to
ensure - matching
● both should undergo the same diagnostic evaluation to
determine presence or absence of the disease under
investigation
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Advantages:
● relatively inexpensive and can be completed in a shorter

timeframe than cohorts
● reduce the need for large sample sizes
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Disadvantages:
● Historical data obtained from medical records may be inaccurate or

incomplete
○ equal distribution of patients' ability to recall events that have happened in
the past between the two groups may not be ensured
○ recall bias - patients with disease have probably contemplated factors they
believe may have contributed to disease development
● Unblinded investigators who collect data also may question individuals
exposed to the disease more intensely than control subjects
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Disadvantages:
● information about the exposure and outcome is collected

simultaneously, so it is difficult to sort out the temporal
relationship between the two
○ protopathic bias - difficulty to determine if the outcome preceded the exposure
○ Ex: Abnormal vaginal bleeding may be an early sign of uterine cancer. Vaginal
bleeding, however, may lead to prescribing hormonal therapies such as progesterone.
An investigator may later erroneously conclude that use of progesterone was
associated with development of uterine cancer, when in fact the cancer preceded use of
the progesterone in this case.
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● Odds ratios - used to help interpret the results from
case-control studies
○ an estimate of relative risk
○ greater than one denotes increased risk, equal to one indicates no effect, and
less than one indicates a protective effect
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Cross-Sectional Studies
● prevalence surveys
● can be thought of as a snapshot (or slice) of time because
data are collected and evaluated at a single point in time
● hypothesis generating as opposed to hypothesis testing
● not suited for testing the effectiveness of interventions
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● only an association can be drawn from the results, not a
cause-effect relationship
● quick and easy to perform
● useful for measuring current health status or setting priorities for
disease control
● Ex. a survey of smokers is cross-sectional when the questionnaire is
administered once, even though the questions contained in the
survey may focus on smoking habits over the past 10 years
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● problems are errors in data collection and transient effects that
may influence observations
● inaccuracies in data collection may go unnoticed because there are
no prior data for comparison
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REPORTS WITHOUT CONTROL GROUPS

1. Case studies
2. Case reports
3. Case series
● observational or interventional reports describing patient or patient

group exposure to a drug or technology and can be valuable to record
preliminary findings that lead to further study
● key characteristic to these reports is the lack of a control or comparison
group
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1. Case study
○ a record of descriptive research that documents a
practitioner’s experiences, thoughts, or observations
related to the care of a single patient
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2. Case report
○ a descriptive record of a single individual (case report) in
which the possibility of an association between an
observed effect and a specific intervention or exposure
(often an unexpected complication of treatment or
procedure) based on detailed clinical evaluation and
history of the individual
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3. Case series
○ a group of records (case studies) that documents a
practitioner’s experiences, thoughts, or observations
related to the care of multiple patients with similar
medical situations
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● useful for early recognition of drug toxicities and
teratogenicity
● when possible, results should be confirmed with randomized
controlled clinical trials
● serve as an important initial step in the formulation of
hypotheses
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SURVEY RESEARCH
● is information gathered from an identified group with
conclusions drawn and applied to a larger population
● considered either descriptive (such as opinions and attitudes)
or explanatory (such as explaining a cause and effect) in
nature
● validity of the results depends on the quality of the study’s
internal rigor
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SURVEY RESEARCH
● used to study the incidence, distribution, and relationships of
sociologic and psychological variables
● used to collect information from a sample and generalize the
findings to a larger, target population
● to identify, assess, and compare respondents’ ideas, feelings,
plans, beliefs, and demographics
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SURVEY RESEARCH
● used to determine how health care programs should be
implemented by utilizing the opinions of experts with
experience in a particular area
● to study effectiveness of a program by surveying individuals
who have used its services,
● to understand attitudes and behaviors of patients or members
of the profession the program affects
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SURVEY RESEARCH
● Types:
1. descriptive surveys
■ attempt to identify psychosocial variables such as
attitudes, opinions, knowledge, and behaviors in a
population
2. explanatory surveys
■ attempt to explain causal relationships between
variables
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SURVEY RESEARCH
● Types of data collected:
1. Incidence
2. Attitudinal
3. Knowledge
4. Behavior measurements
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SURVEY RESEARCH
1. Incidence
■ try to determine the occurrence of events without
drawing any relationships between variables
■ morbidity or mortality data, manpower data
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SURVEY RESEARCH
2. Attitudinal
■ try to compare this dependent variable with
independent variables such as age, education, or salary
■ job satisfaction surveys
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SURVEY RESEARCH
3. Knowledge
■ attempt to document a person’s knowledge or level of
understanding about a specific topic
■ physician’s knowledge of retail prices of medications
or pharmacist’s knowledge of state pharmacy laws
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SURVEY RESEARCH
4. Behavior
■ documents what a person actually does in a particular
situation rather than asking him or her in a survey,
which may reflect an attitude, rather than the actual
observed behavior
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SURVEY RESEARCH
● Data collection:
○ questionnaires, examination of historical records,
telephone interviews, face-to-face interviews, Web-based
questionnaires, focus groups, or panel interviews
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SURVEY RESEARCH
● Characteristics of well-conducted survey:
○ objective and carefully planned, data are quantifiable, and
subjects surveyed are representative of the target
population
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SURVEY RESEARCH
● Errors affecting Precision and Accuracy
1. Coverage Error
■ a bias in a statistic that occurs when the target
population you want to survey does not coincide with
the sample population that is actually surveyed
■ can compromise the ability to generalize study results
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SURVEY RESEARCH
2. Sampling Error
■ refers to the difference between the estimate derived
from a sample survey and the true value that would
result if a census of the entire target population were
taken under the same conditions
■ occurs when the researcher surveys only a subset
(sample) of all possible subjects within the population
of interest
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SURVEY RESEARCH
3. Measurement error
■ occurs when the collection of data is influenced by the
interviewer or when the survey item itself is unclear
from the respondent’s point of view
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SURVEY RESEARCH
4. Nonresponse Error
■ occurs when a significant number of subjects in a
sample do not respond to the survey
■ nonresponse bias can result in surveys, where the
answers of respondents differ from the potential
answers of those who did not answer
■ strive for response rates in the 80% to 90% range
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SURVEY RESEARCH
● Evaluation of Survey
1. Factual Data and Internal Validity
■ There must be attempts to assess validity and
reliability of the survey and efforts made to validate
factual data
■ asking more than one question about a concept can
increase the internal validity of a survey
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SURVEY RESEARCH
■ correlation analysis such as the Cronbach alpha or
similar statistical test that measures correlation
between items should be calculated and the
coefficient factor(s) reported in the article
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SURVEY RESEARCH
■ coefficient alpha is interpreted in the same fashion
that coefficients of reliability are interpreted (i.e., 0
indicates no consistency between responses while
increasing consistency is seen as you approach 0.8 to
1)
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SURVEY RESEARCH
2. Sample Size
■ methods section should report sample size, along with
a description of how it was determined
■ will give sufficient statistical power to demonstrate a
difference between two groups
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SURVEY RESEARCH
2. Sample Size
■ investigators must then determine the minimum
number of subjects that must be sampled for the
sample to be representative of the entire population
● made by consulting references that describe
variability in sampling or consulting a statistician
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SURVEY RESEARCH
3. Sample Frame
■ describes the population that will actually be drawn
from to make up the survey sample
■ a sample is comprehensive if all members of a
population had a chance to be chosen and no one was
systematically excluded
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SURVEY RESEARCH
4. Sampling Strategy and Response Rates
■ methods section should supply the reader with
enough information to ensure that nonresponse error
was assessed and measures were taken to control the
error
■ authors should relate as much information about
nonresponders as possible
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SURVEY RESEARCH
4. Sampling Strategy and Response Rates
■ methods section should supply the reader with
enough information to ensure that nonresponse error
was assessed and measures were taken to control the
error
■ authors should relate as much information about
nonresponders as possible
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SURVEY RESEARCH
4. Survey Instrument Reliability
■ assess the reliability (i.e., can the results of the survey
be repeated by another investigator) of the survey
instrument and present the results of reliability
estimates
■ a statistical test that measures correlation between
items should be used as a reliability estimate
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SURVEY RESEARCH
4. Survey Instrument Reliability
■ a pretest or pilot test is an assessment of a
questionnaire made before full-scale implementation
to identify and correct problems such as faulty
questions, flawed response options, or interviewer
training deficiencies
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POSTMARKETING SURVEILLANCE STUDIES

● phase IV studies that follow drug use after market approval
and are sometimes referred to as pharmacoepidemiologic
studies
● useful in identifying new, potentially serious effects of drugs
● allow assessment of drug use outside of product labeling and
may identify areas for further research
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POSTMARKETING SURVEILLANCE STUDIES

● most of the information on postmarketing safety of the
product comes from spontaneous adverse reaction reports
○ monitored for increases in frequency of certain events or
the appearance of serious unexpected events
○ product labeling may be changed to reflect either new
events or events with increasing frequency
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REVIEW ARTICLES
1. narrative (nonsystematic) review (qualitative review)
2. systematic review (qualitative review)
3. meta-analysis (quantitative review)
○ the only type of review providing new quantitative data
derived from combining the results of each study in the
meta-analysis and performing a statistical analysis on that
data set
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REVIEW ARTICLES
● classified as tertiary literature
○ except for meta-analyses which are classified as primary
literature since they create new data
● may be subject to author biases or inaccuracies in the
literature search
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REVIEW ARTICLES
1. narrative (nonsystematic) review (qualitative review)
○ summary of research that lacks a description of
systematic methods
○ may pertain to one specific clinical question or disease
state, or to topics related to pharmacy administration
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REVIEW ARTICLES
○ scientific investigations with predefined methods and
original studies as their subjects
○ summary of results of primary studies where the results
are not statistically combined
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REVIEW ARTICLES
○ publication bias - when published studies are given more
consideration because they are positive in nature than
unpublished studies
■ drawback of unpublished studies - have likely not
undergone a peer-review and revision process; errors
and unclearly stated conclusions may be present
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REVIEW ARTICLES
○ language bias - only articles published in the author’s
primary language are used
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REVIEW ARTICLES
○ To reduce selection bias, authors must be blinded to:
1. names of the study authors (to avoid political or
personal issues)
2. institution of publication
3. results of the studies
○ For the initial choice of study inclusion, only the methods
section should be reviewed
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REVIEW ARTICLES
○ widely used to provide supporting evidence for clinical
decision making
○ results of previously conducted clinical trials are
combined and statistically analyzed
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REVIEW ARTICLES
Types of Meta-Analyses
1. pair-wise meta-analysis
○ traditional method of synthesizing the results of
different trials to obtain an overall estimate of the
treatment effect of one intervention relative to the
control
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REVIEW ARTICLES
Types of Meta-Analyses
2. network meta-analysis
○ multiple treatment comparison or the mixed
treatment meta-analysis
○ a network of randomized controlled trials is
developed where all these trials have one
intervention in common
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REVIEW ARTICLES
Uses
1. supporting or refuting lesser quality evidence

2. overcoming reduced statistical power of small studies
3. assessing occurrence of rare events
4. providing guidance with limited/conflicting data
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REVIEW ARTICLES
Uses
5. displaying sample sizes and treatment effects graphically

6. assessing heterogeneity between studies and publication
bias
7. evaluating the natural history of disease
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REVIEW ARTICLES
Uses
8. improving estimates of effect size

9. answering new questions not posed at the start of
individual trials
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REVIEW ARTICLES
Issues
1. Publication bias
○ studies that show lack of efficacy are less likely to
be located than those that demonstrate beneficial
effects of a drug
○ identified by funnel plots
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REVIEW ARTICLES
Issues
1. Publication bias
○ funnel plot is a scatterplot of treatment effect
versus sample size of the studies included in the
meta-analysis
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REVIEW ARTICLES
Issues
1. Publication bias
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REVIEW ARTICLES
Issues
2. Presence of Divergences
○ heterogeneity (differences in the way the studies
being included in the meta-analysis were
conducted)
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REVIEW ARTICLES
Issues
2. Presence of Divergences
○ publication bias (tendency of investigators to
preferentially submit studies with positive results
for publication)
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REVIEW ARTICLES
Evaluation
1. define the clinical question

2. hypothesis should be stated
3. detailed protocol be developed
4. details of literature searches be given
5. criteria for inclusion must be determined
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REVIEW ARTICLES
Evaluation
6. studies should be similar enough (also referred to as

homogeneity) to allow pooling
7. randomization techniques, compliance, blinding,
appropriate dosing and length of studies, and ITT
analyses
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REVIEW ARTICLES
Evaluation
● common statistical tests used to combine the data

○ Mantel-Haenszel test for categorical data
○ Inverse Variance test for continuous data
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REVIEW ARTICLES
Evaluation
● method to present results obtained from meta-analyses is

the forest plot
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REVIEW ARTICLES
Evaluation
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REVIEW ARTICLES
Evaluation
● sensitivity analysis
○ done on any articles that seemed to not be as
similar as the others combined
○ once identified, analyses are repeated without each
of those suspicious articles
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REVIEW ARTICLES
Evaluation
● sensitivity analysis
○ to determine if this changes the overall results or
conclusions
○ to confirm the accuracy of the results produced by
the meta-analysis
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REVIEW ARTICLES
● should be interpreted with caution
● remember that conclusions depend on the quality and
similarity of the studies included
● oversimplification may lead to inappropriate conclusions
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PRACTICE GUIDELINES
Types:
1. evidence-based
2. formal consensus-based
3. mixture of EBM and consensus-based
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PRACTICE GUIDELINES
Types:
1. evidence-based
● utilize a rigorous systematic process involving review and
critical evaluation of the medical literature to develop
final recommendations
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PRACTICE GUIDELINES
Types:
2. formal consensus-based
● utilize experience of experts in their practice area to draw
conclusions and develop recommendations
● useful for those instances where the evidence does not
exist, is not complete, or not conclusive enough to allow
the development of a final recommendation
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PRACTICE GUIDELINES
Types:
3. mixture of EBM and consensus-based

● uses evidence to construct the guideline and supplements
those steps without evidence with experience of the
experts
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PRACTICE GUIDELINES
● created primarily for:
○ facilitating clinical decision making
○ improving the quality of health care
○ providing consistent treatment across environments
○ decreasing costs
○ diminishing professional liability
○ identifying individualized alternative treatment
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PRACTICE GUIDELINES
● provide information regarding therapeutic options and most
appropriate choices for a specific disease and patient
● research has shown that within 2 years of development, a
practice guideline may become outdated
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Health Outcomes Research

● encompasses literature pertaining to discussion
of pharmacoeconomic, therapeutic, and
nontherapeutic outcomes (such as number of
visits to the emergency room and number of
hospital admissions), along with QOL outcomes
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● QUALITY-OF-LIFE MEASURES
○ patient’s perception of well-being
○ multidimensional concept focusing on impact
of a disease and treatment relative to the
well-being of a patient
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The value assigned to quality and quantity of life
affected by many different variables including
disease, injury, treatment, or policy is termed
health-related quality of life (HR-QOL) and is used
to assist in decision making regarding interventions
such as procedures and pharmacotherapy.
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Two types of HR-QOL measurements:
1. Health status assessment

○ self-assessment that measures multiple aspects of a
patient’s perceived well-being
○ assessment is primarily designed to either compare
groups of patients receiving different treatments or effect
of a treatment for a single group over time
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1. Health status assessment

○ most often used in clinical trials comparing treatment
regimens
○ questions used range from perceived impact of disease
and treatments to disease frequency and severity
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2. Patient preference assessment

○ reflect an individual’s decision-making process at a time
when the eventual outcome is unknown
○ measures the patient’s trade-off between quality and
quantity of life
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Dietary Supplement Medical Literature

The principles and criteria used to analyze the quality of drug
literature are used to analyze DS literature; however, unique
additional points such as standardization and purity must be
considered.
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STANDARDIZATION
● control of the amount of one chemical entity, either an active

constituent (if known) or a marker compound (allow
estimation of levels of other, less-easily assayed chemicals), is
used to standardize the supplement
● allows for uniformity between study product and marketed
product as well as between various brands of one product
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STANDARDIZATION
● plant parts are important

○ If a trial evaluated use of a herb’s root, but the product
about which a practitioner is searching for information
contains the herb’s leaves and flowers, the results cannot
be extrapolated.
RAMOS, RHONA

INTERNATIONAL TRIALS AND INFORMATION
RETRIEVAL
● Appropriateness of generalizing results to a practitioner’s

own patient population must always be considered, just as
with prescription drug trials.
RAMOS, RHONA

TRIAL DURATION
● duration of therapy is important for accurate assessment of

efficacy and safety
RAMOS, RHONA

TRIAL SIZE
● small-sized groups may not have adequate statistical power to

detect a potential difference between a DS and a placebo, if
one truly exists
RAMOS, RHONA

MINIMAL EVIDENCE
● Many products have only animal, in vitro, or theoretical data

to support their claims.
● Without a body of human data, practitioners must often
make counseling or recommendation decisions based on
safety and efficacy data that are theoretical, from case reports
or flawed trials, or from animal and/or in vitro studies.
RAMOS, RHONA

QUALITY AND PURITY
● DSs can be adulterated with heavy metals or prescription

medications
● When a product meets the quality standard, the company
may use, for a fee, a seal of approval on DS labels
RAMOS, RHONA

OTHER SPECIAL CONSIDERATIONS
● DSs are not legally required to be reviewed and approved by

the FDA for safety and efficacy prior to marketing
● FDA can take action if problems are discovered with either,
once a product is available to consumers
RAMOS, RHONA

OTHER SPECIAL CONSIDERATIONS
● DS use continues to be prevalent despite fluctuations in ages

or ethnicities choosing to use supplements and changes in
the popularity of specific products
● Health practitioners must serve as reliable and approachable
information resources for DS information just as they do for
other medications
RAMOS, RHONA
An understanding of strengths and limitations

inherent with each design is essential to
determine the overall quality of the evidence
produced. Those trial designs with a high level
of quality provide the most reliable evidence
and that translates into the strongest
recommendation/clinical decision.

Research Designs

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Research Designs

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CRUZ, CHARLIEMAIGN STANLEY

Although the randomized controlled trial is

the most frequently used study design for

Variations of Controlled Clinical Trial

NON-INFERIORITY (NI) TRIALS

NON-INFERIORITY (NI) TRIALS

● Superiority trials - the aim is to determine that one drug is

NI TRIALS - STATISTICAL RATIONALE

NI TRIALS - STATISTICAL RATIONALE

● Assay Sensitivity - the reference drug being used must have

NI TRIALS - STATISTICAL RATIONALE

● Constancy Assumption - important parameters from

ADAPTIVE CLINICAL TRIALS

Stability Studies/In Vitro Studies

● in a bioequivalence trial, a 10% difference between products would be equivalent,

Observational Study Design

1. prospective (looking forward in time)/concurrent

3. ambidirectional (looking both forward and backward in time)

1. open or dynamic - participants may enter or leave based on changing

3. closed - involves an unchangeable event

● relatively inexpensive and can be completed in a shorter

● Historical data obtained from medical records may be inaccurate or

● information about the exposure and outcome is collected

REPORTS WITHOUT CONTROL GROUPS

● observational or interventional reports describing patient or patient

REPORTS WITHOUT CONTROL GROUPS

REPORTS WITHOUT CONTROL GROUPS

REPORTS WITHOUT CONTROL GROUPS

REPORTS WITHOUT CONTROL GROUPS

POSTMARKETING SURVEILLANCE STUDIES

POSTMARKETING SURVEILLANCE STUDIES

1. supporting or refuting lesser quality evidence

5. displaying sample sizes and treatment effects graphically

8. improving estimates of effect size

1. define the clinical question

6. studies should be similar enough (also referred to as

● common statistical tests used to combine the data

● method to present results obtained from meta-analyses is

3. mixture of EBM and consensus-based

Health Outcomes Research

Health Outcomes Research

Health Outcomes Research

Health Outcomes Research

1. Health status assessment

Health Outcomes Research

1. Health status assessment

Health Outcomes Research

2. Patient preference assessment

Dietary Supplement Medical Literature

Dietary Supplement Medical Literature

● control of the amount of one chemical entity, either an active

Dietary Supplement Medical Literature

● plant parts are important

Dietary Supplement Medical Literature

● Appropriateness of generalizing results to a practitioner’s

Dietary Supplement Medical Literature

● duration of therapy is important for accurate assessment of

Dietary Supplement Medical Literature

● small-sized groups may not have adequate statistical power to

Dietary Supplement Medical Literature

● Many products have only animal, in vitro, or theoretical data

Dietary Supplement Medical Literature