Drug Information Resources

CHAPTER 4 Drug Information Resources


The pharmacist is the healthcare professional who is the point-person for all drug information. Because it is impossible for any one person to know everything, the pharmacist should be able to know where to get information. In addition to locating the information, the pharmacist must be able to interpret, evaluate, and apply it. Equally important is communication of this information. If a physician asks for information, the pharmacist can likely share the information with the language in which it was discovered. However, if the information is intended to be passed along to a patient, the pharmacist may need to explain it in a way that reflects the patient’s health literacy (explained in further detail in Chapter 6, Patient Education).


I. Hierarchy of Pharmacy and Medical Literature
A. Primary
1. Original journal articles

2. Case reports

3. Descriptive reports

4. Expert communication

5. Unpublished literature

6. Peer-reviewed journals
a) New England Journal of Medicine

b) Journal of the American Medical Association (JAMA)

c) Annals of Internal Medicine

7. Non–peer-reviewed journals
a) Supplements

b) “Throw away” journals

8. Advantages
a) Most timely

b) Provides vital information on which therapeutic decisions are based

9. Disadvantages
a) Cost (e.g., cost of journal subscriptions)

b) Access

c) Inconsistencies (e.g., conflicting journal articles)

d) Requires basic statistic knowledge to interpret study design and results

B. Secondary
1. Abstracting and indexing systems of primary literature

2. Medline

3. EMBASE

4. International Pharmaceutical Abstracts (IPA)

5. Advantages
a) Organizes volumes of literature

b) Versatile

c) IPA is a more pharmacy-specific database

6. Disadvantages
a) Cost (e.g., EMBASE is more than $40,000/year)

b) Access

c) Scope (some systems may search more or different journals so not always comprehensive)

7. Medline
a) Abstracting service created by National Library of Medicine

b) Uses MeSH (Medical Subject Headings) terms

c) PubMed is a free search engine for accessing Medline

C. Tertiary (Table 4-1)
1. Assembled information or interpretations of primary literature

2. Textbooks

3. Drug compendia

4. Full-text electronic books and databases

5. Review articles

6. Internet sources of various levels of reliability: It is critical to educate patients about web sources that provide misinformation.

7. Advantages
a) Access

b) Compactness

c) Conciseness

d) Cost

e) Ease of use/easy to read

8. Disadvantages
a) Timeliness

b) Errors in transcription

c) Incomplete detail

II. Components of a Clinical Trial
A. Population
1. Sample: subset of the population
a) Individuals from whom data are collected for the study

2. Sample size/power analysis
a) Determination of the number of patients required to adequately power a study
(1) A large sample size can detect a small difference.

(2) A small sample size can detect a large difference.

3. Randomization
a) Blocked

b) Stratified

c) Cluster

d) Systematic assignment

B. Baseline assessment

C. Study location
1. Single center: use of one site to conduct a research study

2. Multicenter: use of multiple sites to conduct a research study

3. International: use of multiple countries to conduct a research study

D. Blinding
1. Single blind: patient masked, or investigator masked, but not both

2. Double blind: patient and investigator masked

3. Open label: no masking; all patients and investigators aware of treatment

E. Controls
1. Placebo controlled: administration of an inactive substance for a control

2. Double dummy: use of multiple controls to maintain blinding
a) Example: To compare two medicines, one presented as blue tablets and one as red capsules, researchers could also supply blue placebo tablets and red placebo capsules so that both groups of patients would take one blue tablet and one red capsule

3. Active control: use of an established therapy as the comparative group

4. Crossover: patients serve as their own control by receiving multiple interventions

F. Methods

G. Institutional review board (IRB), ethics committees

H. Intervention, duration of treatment

I. Monitoring

J. Follow-up

K. Compliance
1. Measure of adherence

L. Outcome Measures
1. Primary/secondary endpoints

2. Surrogate endpoints: easily measured substitute markers in place of more clinically meaningful endpoints (e.g., CD4 count used as a surrogate endpoint for a trial regarding HIV infection)

M. Statistics
1. Goal: to be confident that the probability statement (p value) is valid and to maximize the possibility of detecting a difference when one actually exists1

N. Results

O. Reporting adverse effects (MedWatch)

III. Assessing Trial Results
A. Findings related to primary outcomes
1. What type of data are presented?
a) Categorical (qualitative data)
(1) Nominal: named categories (e.g., blood type, gender, race)
(a) Mutually exclusive

(2) Ordinal: ordered categories of data; often sequenced (e.g., poor, good, excellent)
(a) Mutually exclusive

b) Numerical (quantitative data)
(1) Continuous: ordered, sequenced, and has a set of distance or values between rank (e.g., blood pressure, glucose levels)

B. Were the findings statistically significant?
1. Hypothesis testing
a) Tests against the null hypothesis
(1) Null hypothesis (Ho): states that the variable of interest is equal to a given value or that no relationship exists between various variables

2. Statistical and clinical significance
a) Statistical: probability that the results are due to chance or due to a true effect of treatment

b) Clinical: importance of the practical relevance or variation of a difference in outcomes
(1) A statistically significant outcome may not be clinically significant

3. P value
a) The probability of the observed result or a more extreme result occurring by chance alone

b) The probability of the observed difference occurring if the null hypothesis is true

4. Types of error
a) Type I error (false-positive error)
(1) Rejecting the null hypothesis when it should be accepted

(2) Relates to validity

(3) Alpha level
(a) It is the risk of finding a difference when there is not one (risk of experiencing a type I error)

(b) Usually 5% by designation, indicating there is a less than 5% possibility that a finding is due to chance (does not really exist)

b) Type II error (false-negative error)
(1) Accepting the null hypothesis when it should have been rejected (there was a difference that was not detected)

(2) Relates to power

(3) Beta level
(a) The chance researchers are willing to risk that a difference will not be detected

(b) The probability of committing a Type II error

(c) Type II error (or beta)

(d) Usually 20% by designation

5. Confidence interval (CI)
a) The range of values in which researchers can be certain that the true point estimate will fall

b) 95% CI most commonly reported
(1) 95% probability that the true result lies within the range of results found, and there is a 5% probability that the true range lies outside the interval

c) CI is calculated by subtracting from and adding to the sample mean the appropriate number of standard errors of the mean

d) The narrower the CI, the greater the reliability and more precise the data

C. How large is the treatment effect (when the primary outcome shows a statistically significant difference)?
1. Relative risk (RR)
a) The reduction in the risk from one therapy relative to another (RR = events in treatment group ÷ events in placebo group)
(1) A RR of 1 means that there is no difference.

(2) A RR that is <1 (e.g., 0.75) means that risk is decreased

(3) A RR that is >1 (e.g., 1.15) means that risk is increased

b) Commonly used to express the therapeutic benefit of a drug

2. Absolute reduction risk (ARR)
a) The absolute difference between the probabilities of the treatment event rate and control event rate (ARR = Probability of events in placebo group [PB] − Probability of events in the active treatment group [PA])

b) Expressed as a percentage

3. Number needed to treat (NNT)
a) Number of subjects needed to treat over a defined period of time to experience one benefit of therapy

b) NNT = 1/ARR

IV. Evaluating Clinical Trials
A. Questions to consider
1. Why was this study conducted?

2. Were previous trials conducted?

B. Consider the power/significance of the study
1. Statistically

2. Clinically

C. Critique the trial
1. Population

2. Intervention

3. Endpoints: were they appropriate?

4. Statistics
a) Consider the appropriateness of each statistical test and result

D. Can the findings from this study be extrapolated to patient/consumer?

V. Study Types in Clinical Research
A. Randomized controlled trial
1. An experiment in which investigators assign, by random allocation, eligible subjects into intervention groups to receive or not to receive one or more interventions that are being compared

2. Gold standard: Randomized controlled trials are considered to have the highest validity and reliability of various research designs, as they eliminate causes of bias and provide a high level of experimental control.

3. Necessary for Food and Drug Administration (FDA) approval

B. Cohort studies
1. Group of subjects who have not yet experienced the outcome of interest

2. Subjects exposed to a factor of interest are compared to a group not exposed and followed prospectively over time

C. Case-control studies
1. Subjects with a particular characteristic are compared to a similar group without the characteristic to determine the cause

2. Retrospective

D. Case reports
1. No control

2. No designed intervention

3. Descriptive account of a subject

E. Meta-analysis
1. A method of combining results of previous and similar research to determine a single estimate of treatment

F. Cross-sectional studies
1. Measurements taken at a single point in time

G. Survey
1. Research used to study the incidence, distribution, and relationship

H. “N-of-1” trials
1. Randomized controlled study involving a single subject

2. Crossover design

3. Lack of generalizability to a population

VI. Research involved in the FDA Drug Approval Process
A. Preclinical research
1. Goal: assess potential therapeutic effects

2. Does not predict human response

B. Phase I
1. Initial study, usually in healthy human volunteers

2. Small number of subjects (fewer than 100 subjects); brief length of study (less than 1 year

3. Determines toxicology, metabolism, and pharmacologic activities; early evidence of effectiveness

C. Phase II
1. Expanded drug study to obtain preliminary efficacy data and safety in humans

2. Small and highly homogeneous population of patients for whom the drug is intended (N = several hundred participants)

D. Phase III
1. Pivotal trials

2. Larger study (N = hundreds to thousands of participants)

3. Long-term (up to several years)

4. Semidiverse population (representing target population)

5. Establishes final formulation, marketing claims, product stability, packaging, and storage concerns

6. Successful completion may mean ready to submit compound to FDA for approval

E. Phase IV (postmarketing surveillance)

F. New Drug Application (NDA) form

G. Abbreviated NDA (aNDA) form: generic drug approval

H. Supplemental NDA (sNDA): approval for new indication

Table 4-1 Common Examples of Tertiary Literature (NOTE: lists are not comprehensive)



























Topic of Interest Literature in which to Find Topic
Alcohol/sugar/gluten free Red Book (Drug Topics)
Adverse effects Meyler’s Side Effects of Drugs Drug-Induced Diseases
Bioequivalence Orange Book (electronic version on FDA website)
Compounding
Remington’s Pharmaceutical Sciences

Extemporaneous Formulations
Consumer health information
USP DI Vol II: Advice for the Patient (obsolete)

Clinical Pharmacology

Lexi-Comp

Micromedex

Websites:

www.drugdigest.org

www.webmd.com
Diseases/General Medicine
Cecil Textbook of Medicine

Harrison’s Principles of Internal Medicine

Dosing

Dosing: Special populations
AHFS Drug Information

Clinical Pharmacology

Drug Facts and Comparisons
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Jun 21, 2016 | Posted by in PHARMACY | Comments Off on Drug Information Resources

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