Clinical Pharmacy 4th Pharm D

1. CRITICAL EVALUATION OF DRUG INFORMATION AND
LITERATURE
PHARM-D 4TH YEAR
CLINICAL PHARMACY
Dr. Pradeepthi.k
Assistant Professor
Department of Pharmacy Practice

2. A) BASICS LITERATURE EVALUATION SKILLS
These are essential in many areas of pharmacy practice.
Pharmacists are faced with an increasingly literate patient
population who educate themselves about drug therapy by
consulting various individuals (e.g., health care professionals,
surveyors of alternative medicine, family, and friends),
searching the Internet, and reading both the medical literature
and lay press.
Such patients often seek the advice of a pharmacist to interpret
information they have obtained.
Likewise, physicians and other health care professionals often
contact pharmacists for opinions regarding various aspects of
therapy.
Unbiased responses to these inquires can only be provided after
careful analysis of available studies.
In addition, decisions on drug policy management, such as
whether to add or delete a drug from the formulary, should be
based on careful review of the literature.

3.  Currently there are more than 25,000 biomedical journals which
are published annually. With such a vast number of medical
literatures available the job of the
 Drug Information Specialist is too demanding and requires lot of
skill to evaluate the available drug information.
 Continuing education programs and symposia help pharmacists
keep up with this information;
 however, these resources may be subject to the bias of the
author, sponsor of the program, or the literature used to prepare
the programs or symposia.
 Pharmacists, therefore, must learn to systematically review and
critique the biomedical literature.
 Skills in literature evaluation enable pharmacists to efficiently
and effectively determine which treatment options represent
therapeutic advances and which lack the potential to improve
patient care and perhaps may even be harmful

4.  (i) Evaluating Controlled Clinical Trials (True
Experiments) In a clinical trial or true experiment,
researchers administer a drug or treatment and follow
the subjects forward in time (prospectively) to determine
the effects of such treatment. Randomized controlled
clinical trials, a type of true experiment, are the gold
standard for determining cause and effect relationships.
 ) Journal, Investigators, Research site and Funding The
first step in the literature evaluation process begins by
briefly scanning the article.. The study should be
published in a reputable journal where manuscripts
undergo peer review before publication.

5.  Studies that fail the peer-review process may be
submitted to alternate journals for consideration.
 If the research topic seems out of place for a particular
journal, this may be an indication that the study was
initially rejected for publication by peer reviewers from
more pertinent journals.
 Clinical studies are rarely, if ever, published in "throw-
away" journals. Throw-away journals are characterized by
being free to readers, having a high advertisement-to-text
ratio, not being owned by professional societies, having a
variable peer-review process, and not having a section for
critical correspondence.
 Article published in such journals are of little benefit in
clinical decision making

6.  (b) Title /Abstract The title of the article should be brief and
catch the attention of readers
The title of the topic.
 The title should also be unbiased and should t indicate
author's preferences for any particular drug treatment.
 The abstract briefly describes the purpose, methods,
results, and conclusion The abstract briefly. By scanning
the abstract, readers should be able to determine whether
the study is of interest and deserves further review
Abstracts should be clearly written.

7.  (c) Introduction The introduction part of a clinical study
contains background information for the study; states
study objectives and hypotheses, and indicate any
planned subgroup or covariate analyses.
 This part also addresses ethical issues related to
conduct of the study.
 Sufficient background information should be provided to
demonstrate that the study is important and ethical.
 Current treatment paradigms for the disease state being
studied; limitations of these treatments, and reasons why
the treatment under investigation may offer benefits
should be discussed.
 Data from completed preclinical and / or clinical studies
should be summarized to justify that further study in the
area is needed. Background information should indicate
that potential benefits outweigh risks to subjects entering
the study.

8.  (d) Methods Study methodology is the most important
section of a clinical study. The methods section contains
information on the design, study population,
instrumentation, and statistics used for the investigation.
Results of studies with serious methodological flaws may
be unreliable. The methods section should be sufficiently
detailed to allow investigators to reproduce the study.
Additionally, authors should state that the protocol is
available upon request in case readers have additional
questions regarding study methodology.

9.  Parallel Versus Cross-Over Studies
 In a parallel study, subjects receive only one treatment,
while during a cross- over study; subjects receive all
study drugs during the course of the study. Parallel
studies are most appropriate when therapies are
definitive or when disease states are self-limited (e.g.,
antimicrobials for infectious diseases). When disease
states are chronic and / or highly variable (e.g.,
glaucoma, migraine headache), cross-over designs are
more appropriate.

10.  Important points to be considered in Cross-Over
Studies:
 Wash out period must be of sufficient duration to prevent
carry-over effects
 Multiple cross-over periods are useful when studying
diseases with exacerbations and remissions.
 Subjects should be randomized to treatment order.
 Both investigators and subjects should be blinded to
time when cross- over occurs.
 Subject drop-outs and deaths should be minimized.

11.  Inclusion and Exclusion Criteria
 Inclusion and exclusion criteria describe the study
patients. Inclusion criteria list subject characteristics that
must be present for enrollment into the study and
exclusion criteria list characteristics that, if present,
preclude enrollment into the study inclusion and
exclusion criteria must be carefully stated so readers can
assess whether the study sample is representative of the
population to which the results are intended to be
generalized. Diagnostic criteria for disease states should
be clearly defined.

12. SAMPLE SIZE
 A sample is a subgroup from the entire population
of patients with a particular disease state who
would be eligible to enter the study. Samples are
used because of logistic, financial, and resource
constraints that prohibit studying entire population.
Sample size is very important while evaluating
clinical studies. Sample size varies from study to
study based on the factors discussed below...
 If the sample size is too small type II error can
occur i.e. false negative result is likely. The sample
may not represent population. If the sample size is
too large, the results may lack clinical significance.

13.  Determinants of Sample Size
 • Alpha or level of significance (i.e., probability of
false-positive result)
 Beta (i.e., probability of false-negative result)
 Delta (i.e., amount of difference to be detected)
 Standard deviation (i.e., variation)
Controls
 A drug may exert psychological benefits even if it is
pharmacologically inactive. Factors such as the
natural history of the disease, extensive

14.  monitoring and ancillary care, chance, or bias can
influence the efficacy and safety outcomes of clinical
trials.
 Two types of controls are utilized in a clinical trial,
placebo and active. In Two types ofolled trials, the
control appene vaste, leo that is identical to the study
drug in terms of appearance, taste, smell, and other
identiceristics, but does not contain the active
ingredient. Active controls are used when efficacy and
safety of two or more drugs need to be compared or
when it would be unethical to administer a placebo.

15.  Outcome variables
 The clinical outcomes should be relevant, clearly defined,
objective, and clinically and biologically significant. The
researcher / investigator should define variables to be
measured and the amount of difference between
treatment and control groups that the study is designed
to detect Variables should be measured at appropriate
intervals and for an appropriate length of time to ensure
that both positive and negative aspects of a therapy are
adequately assessed. Both the treatment and placebo
groups should be followed with the same intensity.

16.  Randomization
 Randomization is an important aspect of study
design. When studies are randomized, subjects
have an equal and independent chance of receiving
any of the treatment modalities. Randomization is
equivalent to flipping a coin and helps ensure that
treatment groups are similar in regard to clinical
and socio-economic factors that may affect
treatment outcome Randomization helps diminish
patient and investigator bias by prohibiting
investigators from assigning drug treatments
Randomization requires that an unpredictable
treatment sequence be generated that remains
concealed until subjects are allocated to treatment.
Proper meuiods of randomization include use of
random number tables, computer-generated
random numbers, or lotteries.

17.  Randomization can be simple (unrestricted) or balanced
(restricted). Simple randomization is accomplished by
referring to a list of random numbers. Balanced
randomization is sometimes used. For balanced
randomization, blocks of patients (e.g., every 10
consecutively enrolled patients) are randomized to
ensure that similar numbers of patients are allocated to
each treatment group.
 Blinding
 The investigators and subjects who are involved in a
clinical study usually Have an opinion about the therapy
undergoing investigation. The response of the subject
and researcher evaluation may be affected by these
views.

18.  Blinding helps prevent these biases from influencing
study results and ensures that monitoring and ancillary
care is applied equally to both treatment and control
groups Mechanisms for blinding the study and similarities
between the treatment and control (e.g., appearance,
taste, smell) should be described in clinical trial reports
The location of the code and whether or not the blind was
broken during the clinical trial should also be discussed.
 In a single-blind study, either patient or investigators are
unable to identify the treatment (active or control)
assigned; the alternate group (i.e., patient or investigator)
is aware of therapy being administered. In a double-blind
study, neither investigators nor patients are aware of
treatment assignments

19. TYPES OF BLINDING
 Single-blind Either subjects or investigators are
unaware of assignment of subjects to active or
control groups
 Double-blind Both subjects and investigators are
unaware of assignment of subjects to active or
control groups
 Triple-blind Both subjects and investigators are
unaware of assignment of subjects to active or
control groups; another group involved with
interpretation of data is also unaware of subject
assignment.

20.  Data Collection
 Accuracy of measurements taken at study initiation may
differ from those obtained towards study conclusion.
Validation of data collection forms and instruments must
also be undertaken. Accuracy of computer data entry
should be determined periodically by comparing a portion
of patient records to computer printouts.
 Compliance
 Subject compliance may also influence results and should
be evaluated. There are many disadvantages to commonly
used methods of compliance monitoring such as pill counts
and urine or serum drug concentrations, but xitad more
accurate methods such as use of computerized
prescription vials often are not feasible because of their
expense. Monitoring of compliance is

21.  Particularly important in studies where subjects receives
medications on an outpatient basis and are responsible
for self-administration of the stay drugs. If study results
indicate that a treatment is ineffective, but compliancy
drugs study drug was low, lack of therapeutic benefit may
be due to poor compliance of the study subjects rather
than lack of efficacy of the drug therapy.

22.  Statistical Analysis
 Errors in statistical analysis of data are commonly
encountered and invalidate study conclusion.
Statistical tests are based on the study design and
the type of data represented by outcome variable
used for study endpoints. There are four types of
data- nominal, ordinal, interval, and ratio. Nominal
data are categorical (e.g. male/female, complete
response/partial response/treatment failure),
Ordinal data reflect a ranking (e.g., 1+/2+edema,
1/6 to 6/6, heart murmurs), Interval data have
measurable equal distance between data points,
but no absolute zero (e.g., temperature in degrees
Fahrenheit), Ratio data are similar to interval data
except an absolute zero point is present (e.g.,
serum drug concentrations, temperature in degrees
Kelvin).

23.  Each type of data builds on the last, with nominal data
being the weakest and interval/ratio data the strongest.
Categories for nominal data should be specified a priori to
avoid data dredging for statistically significant results at
the conclusion of study.

24. TYPES OF DATA
 Nominal Categorical data
- Examples Yes/No; male/female; response/no
Response/partial response.
 Ordinal: Data reflects ranking
Examples Visual analog scales; Likert scales
 Interval Data with measurable equal distances
between points but no absolute zero
Examples: Temperature in degrees Fahrenheit
Ration Data with measurable equal distances
between points and an absolute zero
Examples Temperature in degree Kelvin; serum drug
concentrations

25.  Statistical tests are either one-sided or two-sided (also
referred to as one- tailed or two-tailed). A one-sided
test is used when the direction of the relationship
between outcome variables is known (i.e., the
variables can only vary in one direction from their
original value).
 A two-sided test is used when the direction is
unknown. For example, consider a drug being
investigated for the treatment of asthma.
 If it is known that the drug will improve pulmonary
function tests (PFTs), a one-sided test can be used;
however, if the drug may either improve or worsen
PFTs, a two-sided test would be used.
 A two-sided test requires a stronger relationship to
achieve statistical significance than a one-sided test
and is therefore often considered the preferred
method. Whether one-sided or two-sided tests are
used for study analysis should be specified a priori.

26.  Results Data should be presented in a clear and
understandable format. Authors. should indicate in
the article how original data can be obtained, if
desired. Confidence intervals and / or p values
should be provided for any statistical analysis
performed on the data. Efficacy results should be
described in sufficient detail for readers to perform
their own analysis of the data, if desired.
 Information on adverse effects should include
severity of the event, how it was managed, and
whether it was believed to be drug related.
Variables that may have affected the prognosis in
the control and treatment groups should be
identified.

27.  If conduct of the study deviated from the protocol, reasons for the
discrepancy should be provided (i.e., investigator error, patient
noncompliance, laboratory error). Data should be presented as actual
numbers, rather than percentage changes alone.
 Type I and Type II Errors A type I error occurs when the investigators
accept the research hypothesis when it is incorrect (e.g., a false-
positive result).
 The probability of a type I error is equal to alpha or the level of
significance and by convention is usually set at .05. When a statistically
significant difference is found between treatment groups at a
significance level of .05 (e.g. p<.05), there is a 1 in 20 probability that it
was a chance finding and does not indicate a true difference between
treatment and control groups.
 For example, consider that the study comparing drug A and drug B in
the treatment of acute otitis media with effusion showed that drug A
was statistically better than drug B in achieving bacteriological cure at
a significance level of .05%. For this study, there is a 95% probability
that these results represent a "true" difference between efficacy for
drugs A and B and a 5% probability that the results are a chance
finding or false-positive result. Type I error is rarely discussed by the
investigators, but should be considered by readers. Study results are
never 100% accurate; there is always the possibility that the results are
a chance finding that would not be replicated if the study were
repeated.

28.  Type Il erors (eg, false-negative realy, office occur
whenever investigator de that two treatments are equally
efflequines equally safe. Ten errors are usually the result of
chance or inadequate sample sizes.

30.  Studies should be analyzed in terms of two types of
validity - internal and external. Internal validity refers to
the extent to which the study results reflect what actually
happened in the study (e.g., are the results consequent
to the drug under investigation or are they the result of
another confounding factor?). Such confounding factors
can include events that develop between initial and final
measurements, changes that occur in subjects during the
course of the study, accuracy of instruments and the
investigators taking measurements, selection of subjects
in a nonrandomized manner, and drop- outs and deaths
that occur during the study resulting in elimination of
important data points.

31.  External validity is the degree to which the study
results can be applied to patients routinely
encountered in clinical practice (e.g., are the
conditions of the study replicable or do factors such
as concomitant medication use and presence of
additional disease states in study subjects make it
impossible to generalize results?). If study
conditions are not similar to those routinely
encountered clinical situations, the results may not
be applicable to patientcare.
 (f) Conclusions forestingia a 18 min The
conclusion/discussion section allows authors to
provide an interpretation of their data and how it
relates to clinical practice. Study conclusions
should be consistent with results and related to the
initial study question. Results should be compared
to a systematic review of all previously published
data.

33. CONCLUSION
 All the Pharmacists must be effective medication
informatigy, providely regardless of their All iter with the
advances in information technology, virtually every
pharm their petities of setting has easy access to disus
information from texts, jounis regardless of practicer
printed media. The pharmacists must achieve a
minimum levels skill in providing drug information
services. This will enhance the ability of pharmacists to
provide comprehensive patient care.
 There is a large need for individuals with special training
as medication information spe There is a large operate
drug information centers and provide leadership in the
area of drug informatics, institution drug policy, poison
control, pharmaceutical industry and academia.
Pharmacy will become an information based profession
as pharmacists develop a comprehensive knowledge
effectively.

34. THANK YOU