Drug Information Resources and Literature Retrieval: Karen L. Kier, M.SC., PH.D., BCPS

Drug Information Resources
and Literature Retrieval
Karen L. Kier, M.Sc., Ph.D., BCPS

Ohio Northern University
Ada, Ohio
Miki Goldwire, M.S., Pharm.D.

Regis University Rueckert-Hartman College
for Health Professions
Denver, Colorado
An excerpt from ACCP’s Pharmacotherapy Self-Assessment Program, 7th Ed., Science and Practice of Pharmacotherapy.
Drug Information Resources and Literature Retrieval
Drug Information Resources

and Literature Retrieval
Karen L. Kier, M.Sc., Ph.D., BCPS

Ohio Northern University
Ada, Ohio
Miki Goldwire, M.S., Pharm.D.

Regis University Rueckert-Hartman College
for Health Professions
Denver, Colorado
An excerpt from ACCP’s Pharmacotherapy Self-Assessment Program, 7th Ed., Science and Practice of Pharmacotherapy.
ACCP Updates in Therapeutics® 2018: Pharmacotherapy Preparatory Review and Recertification Course
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Learning Objectives 2. A physician requests a brief summary of a new anti-

depressant, vilazodone. The pharmacist answering
1. Analyze the most appropriate drug information this question has not heard of this drug. Which one
(DI) resources including primary, secondary, and of the following resources is best to consult for this
tertiary sources for answering questions related to information?
clinical practice. A. MEDLINE, in-process
2. Analyze the similarities and differences of second-
B. IDIS
ary and tertiary information resources for specific
types of drug or medical information. C. PubMed
3. Develop an appropriate search strategy for a given D. IPA
DI question that will result in high-quality litera-
ture retrieval. 3. A MEDLINE search using the MeSH terms for
4. Analyze evidence-based medicine resources and stroke and aspirin is conducted to find information
clinical guideline/trial resources used in the liter- on whether every woman over the age of 55 years
ature retrieval process. should take low-dose aspirin for stroke prevention.
5. Evaluate Web resources related to herbal products, In addition to this approach, which search strategy
product identification, and poisonings. would best minimize the retrieval of erroneous
6. Develop strategies for accessing and searching data?
quality Web-based resources. A. Using the keyword word search of “aspirin
7. Justify the use of valid and reliable Web resources AND stroke”.
by health care professionals and the general public.
B. Using the subheading “therapeutic use”.
8. Develop strategies for accessing informa-
tion pertaining to adverse drug reactions and C. Limiting the sex to “female”.
pharmacovigilance. D. Restricting the publication type to “review”.
4. Which mobile application for a personal digital

Self-Assessment Questions assistant (PDA) or smart phone would most effi-
Answers and explanations to these questions can be ciently and effectively identity if simvastatin,
found at the end of this chapter. benazepril, hydrochlorothiazide, and omeprazole
will interact with clarithromycin?
1. A colleague tells you about a poster on the advan- A. MobileMicromedex.
tages and disadvantages of the Baxter IV pump B. Clinical Pharmacology OnHand.
specifically for pediatric patients in the Intensive
C. Epocrates.
Care Unit (ICU). The poster was presented at an
annual national pharmacy meeting. Which one of D. Lexi-Drugs.
the following sources would be best to find this
poster? 5. A pharmacist is researching MEDLINE for the
dose of gabapentin for treatment of spasticity in a
A. IDIS.
36-year-old woman newly diagnosed with multiple
B. IPA. sclerosis. If using the MEDLINE terms “gabapen-
C. MEDLINE. tin” AND “spasticity,” which one of the following
D. Ovid. limit functions would best help narrow results and
limit erroneous results?
A. Human.
B. English only.
C. Human and English only.
D. Clinical trials.
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6. A medical resident has requested information on a that to date there is no convincing evidence that sele-
recent news story regarding the depletion of mag- nium supplements can prevent cancer in men, women,
nesium by proton pump inhibitors. She requests or children. In addition, the results of the Nutritional
more information as to the clinical presentation as Prevention of Cancer Trial (NPCT) and the Selenium
well as the incidence of this depletion in patients. and Vitamin E Cancer Prevention Trial (SELECT)
Which one of the following would be the best raised concerns about possible harmful effects of sele-
Internet source to find this information? nium supplements.
A. www.clinicaltrials.gov.
8. A 47-year-old man has read recent information that
B. www.fda.gov.
selenium supplementation can decrease his risk
C. www.mayoclinic.com. of prostate cancer. His family history of prostate
D. www.clinicalevidence.com. cancer includes his father, grandfather, and older
brother, who all three developed prostate cancer in
7.
A 54-year-old woman has a 10-year history of their 50s. The patient currently has a prostate-spe-
relapsing, remitting multiple sclerosis. She has cific antigen test with his yearly physical, which
either not tolerated or failed all commercially includes a digital rectal examination of the pros-
available drug therapy options. The patient lives in tate. He takes a daily multivitamin that contains
rural Montana and has limited travel and medical 55 mcg of selenium. Based on the results of the
resources. She is interested in trying to find a clin- Cochrane Review, which one of the following is
ical trial that she might be eligible for that could the best advice for this patient?
provide some other therapeutic options. Which one A. Continue the daily multivitamin that contains
of the following Web sites would provide her with the RDA for selenium.
the best options?
B. Add an additional selenium supplement to the
A. WebMD. multivitamin to reach a daily dose of 200 mcg
B. www.clinicaltrials.gov. per day.
C. www.fda.gov. C. Discontinue the daily multivitamin and
increase his daily selenium to 400 mcg per day
D. www.controlled-trials.com.
with nutritional milkshake supplements.
Questions 8–11 pertain to the following case. D. Discontinue the current brand of multivitamin
The Cochrane Library (Cochrane Database of and find a supplement that does not contain
Systematic Reviews) published a systematic review selenium.
on the use of supplemental selenium in the prevention
of cancer. The review was published in May of 2011 9.
The conclusions of the Cochrane authors seem
and included all pertinent clinical trials as of April 5, inconsistent with the OR reported for both cancer
2011. The review included 49 prospective observational incidence as well as mortality. What is the best
studies and six randomized controlled trials (RCTs). explanation as to why the reviews indicated that
In epidemiologic data, the review reported a reduced there is no reliable conclusion that can be drawn
cancer incidence (odds ratio [OR] of 0.69 (95% confi- between selenium exposure and cancer risk?
dence interval [CI] 0.53–0.91) and mortality (OR 0.55, A. Odds ratios are an estimate of relative risk and
95% CI 0.36–0.83) with higher selenium exposure. the actual relative risks were not provided.
The cancer risk reduction was more pronounced in B. The RCTs showed inconsistent results com-
men (incidence: OR 0.66, 95% CI 0.42–1.05) than in pared with the observational study designs;
women (incidence: OR 0.90, 95% CI 0.45–1.77). The therefore, a causal relationships could not
authors of the review stated that no reliable conclusions concluded.
can be drawn regarding a causal relationship between
C.
The CI showed wide variability and often
low selenium exposure and an increased risk of cancer.
included a value of one, thereby indicating that
They also summarized that the effect of selenium sup-
the data are weak.
plementation yielded inconsistent results in RCTs, and
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D. The potential for sex bias in the observational C. www.controlled-trials.com.

studies created inconclusive results. D. www.guideline.gov.
10. Both the NPCT and SELECT found possible harm- 13. A patient from the anticoagulation clinic has found
ful effects of selenium without additional reduc- a Web site that provides a comparison between
tions in cancer. The NPCT evaluated 200 mcg/ dabigatran and warfarin for atrial fibrillation. The
day in prevention of non-melanoma skin cancers in patient insists on switching to this new therapy
light-skinned participants; the SELECT evaluated because this Web site states that dabigatran is more
the use of selenium 200 mcg/day with or without effective than warfarin and does not require any
vitamin E 400 international units/day in more than blood work. When you inquire about the source
35,000 men older than 55. The SELECT trial cohort of the information, the patient tells you that it is
included 15% African American males. These two called “Dean’s Stroke Musings.” The patient has
RCTs illustrate a potential problem related to inter- read several other Internet testimonials on treat-
nal validity (methodology). Which one of the fol- ment with dabigatran and how it has changed the
lowing was most important to consider when the writer’s life. Which one of the following is the best
Cochrane reviewers were evaluating the data? advise to give this patient on the use of the Internet
A. Variability in dose of selenium. for patient information?
B. Variability in sample size. A. Discourage them from using blogs and patient
C. Publication bias. testimonials for advice.
D. Comparability or homogeneity of samples. B. Caution them on opinion pieces and redirect
them to search the web for other sites.
11. A
student pharmacist is completing an Advance C. Redirect them to WebMD to compare treat-
Practice Rotation and has been assigned the task ments for atrial fibrillation.
of seeing if any additional studies have been pub- D. Redirect them to better sites and provide them
lished on selenium and cancers since the most with some standard questions to help deter-
recent Cochrane Review has been published. mine a high quality site.
Which one of the following is the best resource for
the student to use?
A. PubMed. Abbreviations
B. UpToDate.
C. Google. ADR Adverse drug reaction
AHFS American Hospital Formulary Service
D. www.fda.gov.
CAM Complementary and alternative medicine
CPG Clinical practice guidelines
12. The health care advisory committee to an employee
DI Drug information
wellness program is contemplating adding vitamin
EBM Evidence-based medicine
D serum concentrations to its routine laboratory
HCP Health care professional
screening. The cost of adding this particular test is
IDIS Iowa Drug Information Service
$12 per employee, which is a significant increase in
IPA International Pharmaceutical Abstracts
overall expenditures. The vice president of human
NLM National Library of Medicine
resources is asking the advisory committee to
PDA Personal digital assistant
provide data or national guidelines that show the
PSA Prostate-specific antigen
cost-benefit of this recommendation. Which one of
RCT Randomized controlled trial
the following would be the best reference source to
REMS Risk Evaluation and Mitigation Strategy
start looking for national guidelines or standards?
TCM Traditional Chinese medicine
A. Google.
B. WebMD.
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BPS Pharmacotherapy Specialty Examination Content Outline

This chapter covers the following sections of the Pharmacotherapy Specialty Examination Content Outline:
1. Domain II: Drug Information and Evidence-Based Medicine
a. Task 1, Knowledge statements 2, 3
b. Task 2, Knowledge statements 6,7
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I. OVERVIEW OF DRUG INFORMATION RESOURCES
A. The efficient use of drug information (DI) is an important skill for all pharmacists to have regardless of
their practice site. In all pharmacy settings, pharmacists are recognized as drug experts and as providers of
DI. It is imperative, therefore, that pharmacists know how to provide accurate and complete responses to
DI requests. Keeping current with DI resources is challenging for the clinician because of the vast amount
and the variable quality of available resources. Technology has also brought DI to the patient’s bedside.
Pharmacists should know what DI resources are available and be able to use these sources effectively and
efficiently. The chapter reviews the types of literature used in the synthesis and provision of DI.
B. Primary literature is the most up-to-date resource available to the clinician and consists of journal articles
reporting original research, new ideas, or opinions. These resources are useful for research, education, and
current awareness. Not all articles found in journals are considered primary literature; for example, review
articles that summarize the literature are classified as tertiary resources.
C. Secondary resources include indexing and abstracting systems that organize and provide easy retrieval of
primary resources. Indexing systems include the article citation, with or without access to the abstract; some
include a link to the full-text article. Abstracting systems provide not only the citation but also the abstract
and often a link to the full-text article. Examples of secondary resources include MEDLINE (through
PubMed, EBSCO, Ovid), Academic Search Premier, Cochrane Database of Systematic Reviews, Iowa
Drug Information Service (IDIS), International Pharmaceutical Abstracts (IPA), Embase/Excerpta Medica,
Biosis Previews/Biological Abstracts, CancerLit, SedBase, Reactions, Clin-Alert, Current Contents, and
Toxline. Proper training is required for efficient use of these resources.
D. Tertiary resources are sources that condense and summarize data from the primary literature. These include
not only textbooks and compendia but also electronic databases (e.g., Micromedex, Lexicomp) and review
articles. The best tertiary resources are written by experts in the field and are peer reviewed. If the tertiary
resource is not current or comprehensive, a secondary resource should be consulted to locate primary liter-
ature on the topic. However, some questions can only be answered by using tertiary sources.
II. INTERNET SOURCES OF DI
There has been an explosion of information available on the Internet for both the health care professional and the
consumer. An estimated 60 million U.S. adults use search engines daily basis to explore more than 1 trillion Web
pages; studies suggest that about 60% of adults search for health-related information. According to some top
Internet researchers, the public is unable to find the information they seek almost 50% of the time. The quality
of the information that they do find is a separate concern.
Patients rely on the Internet for health and DI when they may not have access to a knowledgeable health care
professional (HCP). Studies have shown that the younger population will use the Internet as one of their primary
sources of DI. Older adults (60 years and older) prefer to talk to an HCP as their primary source of DI, but these
patients will also access the Internet. Compared with an HCP, members of the public may have fewer skills to
evaluate the validity of the DI that they receive from the Internet. The National Library of Medicine (NLM)
has created a 16-minute video intended to help consumers distinguish a good Internet source of information
(www.nih.gov/MEDLINEplus/webevalu.html). As the video points out, anyone can create an Internet site, and it
is essential to determine the creator of the site, the creator’s credibility, and the way to contact the organization
who has ownership of the site.
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As with any Internet source, pharmacists should evaluate the credibility, validity and reliability of the infor-
mation. Health care professionals can rely on the same NLM concepts provided for consumers when searching
the Internet. Many Internet services, either available free or for a paid subscription, can be invaluable sources
of high-quality, evidence-based medicine. Many sites provide HCPs with fast results to DI questions and even
access to professional journals. The skill of the researcher is essential in getting to the best information, and stud-
ies have documented that skill level can make a difference in the quality of the information obtained, whether
from commercial sites or from free professional sites such as PubMed.
A. Search Engines
When searching for specific words or phrases, a search engine (e.g., Google, Yahoo!, Bing, AOL Search,
Ask) is useful. Different search engines often produce different results for the same term; therefore, the use
of more than one search engine can improve results. For searches that require broad or nonspecific terms,
using an online subject director such as World Wide Web Virtual Library may help identify more appropri-
ate terms. A free resource on Internet searching is available at http://www.SearchingTheInternet.info/.
The Internet does not replace the science of DI retrieval and evaluation. Internet searches retrieve data that
still needs expert analysis and a critical eye to evaluate the evidence. A 2009 study found that search engines
were vastly different and recommended against reliance on a single source. The study also found that search
engines often show Wikipedia results at the top of the results list (referred to as the visible area). Wikipedia
is not peer-reviewed and does not always provide valid and reliable information; its information should be
viewed with skepticism and not relied upon as a major DI source. The study also revealed that the most
valuable or highest quality references for a HCP are usually found in the scroll area, which requires you to
scroll down to other pages to find significantly better results. Other studies have shown that both HCP and
consumers do not typically take the time to look at the resources in the scroll area, and when they do, they
often do not scroll more than two pages.
Another study evaluated the number of paid advertising sites that came up in the visible area after a search.
Of the four sites evaluated, Google had the most sponsored links. The other sites evaluated were Yahoo!,
MSN/Live, and Ask.com. However, Google had the best retrieval when looking at organic URLs (original
Web site) versus a search engine or meta site. This study confirmed the need for good query or research
skills when trying to find the best quality information on the Internet.
1. Boolean Logic
Boolean logic is used in search engines such as Google, StatRef! MEDLINE, and AccessPharmacy.
The use of Boolean operators and, or, and not can help narrow results in search strategies; some search
engines automatically assume and as an operator. Use of two search terms and the operator and tells
the engine to search for both terms. Articles that contain both of these search terms will be chosen.
Two search terms and the operator or will tell the engine that one or both terms must appear within
the record. If not is used, the engine will look for articles that do not contain the search term. Specific
search engines may have different terms for NOT (e.g., Google uses a minus sign). In addition, most
major search engines provide Advanced Search Operators that can be useful for searches on specific
topics. The sites offer ways to restrict searches for a particular site or by a particular author or even by a
particular link to another site. Look at sites for direction (e.g., Google Guide Quick Reference: Google
Advanced Operators, Bing).
2. Advanced Search Keywords
Metasearch engines (e.g., Dogpile, metaCrawlerdogpile, metacrawler, Search.com) allow the user to
enter terms and search multiple search engines at one time. Some of these sites eliminate duplicate
results and provide the user with a list ranked by relevancy. The caveat is that these search engines
can miss valuable information on the Internet. The HCP will be most interested in specialty search
engines specific to health care (e.g., Academic and Scholar Search Engines and Resources [http://virtual
privatelibrary.blogspot.com/Scholar.pdf ], eHealth careBot [www.ehealth carebot.com/]).
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3. MEDLINE MeSH Terms

Medical subject heading (MeSH) terms are a standardized vocabulary used for indexing articles in
MEDLINE; familiarity with these terms is necessary for an efficient and effective search. The MeSH
terms are organized within MEDLINE in a fashion referred to as a tree structure. This hierarchal sys-
tem allows for either broad topic searches (e.g., cardiovascular disease) or more narrow searches (e.g.,
cardiac tamponade). Each MeSH term has its own subheading and subheadings also may have subhead-
ings. When searching, a narrow subheading (e.g., congenital heart defects with a subheading of drug
therapy) or a broad category (e.g., congenital heart defects) that will encompass several subheadings can
be selected depending upon need. Such techniques help to search specific aspect or facet of the topic.
The multiple ways to search MEDLINE include by MeSH term, by keyword, by journal name, by
author, and by title of article. The most efficient search will depend on the type of information is needed.
Keywords are single terms that appear in the title, abstract, and MeSH terms of an article. The disad-
vantage of using keywords is that it may result in a search strategy that is too broad in scope and identi-
fies irrelevant articles. When searching MEDLINE through Ovid or EBSCO, the engine will try to map
keywords to a MeSH term; there may or may not be a suitable corresponding MeSH term. Keywords
are typically used when no MeSH terms are available for a specific concept or when the MeSH term
is not specific enough. For example, if a new drug has just been released but has not been assigned a
MeSH term, a keyword search is the best approach to find articles on that particular drug.
B. Search Strategies
The most efficient search for a particular article often uses the article title or author name. Searching by
journal name can locate a specific article or series of articles in one journal issue. When searching by journal
name, the specific title as indexed by the National Library of Medicine (NLM) is required. Likewise, when
searching by author name, the last name and first initial (or first and second initial) of the author are needed. A
search by article title or author name can be performed with the single citation matcher available in PubMed.
The limit function in MEDLINE provides a means of filtering unwanted articles from a set of search results.
The search parameters are limited according to the criteria the searcher selects. Examples of limits include
language, human or animal species, gender, age group, review articles, latest updates, publication type,
publication year, and local holdings.
C. Obtaining High-Quality DI (B)

Published articles provide helpful tips on how a busy practitioner can search a database such as MEDLINE
and narrow the results to only high quality randomized controlled trials (RCTs). Researchers have found
that the use of filters can provide clinicians with better searching strategies. The two most prominent filters
being researched are content filters and validity filters.
Content filters are specific to the drug or disease state being searched and ensure that the clinician is search-
ing the most appropriate content. For example, an advanced search in PubMed involving MeSH headings will
show that if the search is for regional enteritis, “Crohn’s disease” is a better content filter. In the IDIS system,
the disease index would indicate that “enteritis, regional” would be the more appropriate term. Likewise,
if searching for antibiotics for otitis media, the search term “antibiotics” would not be a good content filter
because the databases are searched for just that term and not necessarily a specific type of antibiotic. PubMed
and MEDLINE allow the researcher to explode terms like antibiotics to get better content results.
Validity filters are a means to narrow the search to only the highest-quality studies. Terms such as “ran-
domized controlled trial” or “double-blind” can be used to eliminate studies of weaker methodology. In a
recent study, pharmacy students provided with content and validity filters demonstrated improved searching
abilities and identified more articles on evidence-based medicine (EBM) than students searching without
these filters. For the busy practitioner, proper training on how to search secondary databases with the use of
content and validity filters can produce DI answers in less time and with better-quality evidence.
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Another consideration in searching the professional literature is that databases such as Google Scholar are
not designed to be comprehensive; therefore, good-quality studies can easily be overlooked. The use of other,
more reliable databases (e.g., MEDLINE, PubMed) is preferred for researching DI questions. A better role
for Google Scholar would be in finding access to full-text articles once a proper search has been done using
other databases or as a complement to other database searches. Google Scholar is also limited by its software
and the algorithms that it uses to search for articles. Researchers have noted that some Google Scholar search
results are questionable, and that the system is negatively influenced by typos and inaccuracies in the data.
This continues to strengthen the need for checking more than one source when researching DI.
III. EVALUATING DI RESOURCES
A. Secondary DI Resources
Secondary sources provide a rapid method by which to search the primary literature. Today most secondary
DI sources are electronic indexing systems that aid users in locating primary literature. These resources
have detailed and user-friendly search engines that enable literature searches on a specific topic. The search
engines employed are extensive and provide immediate results once the details of the system are learned.
Not all secondary resources have the same collection of journals; therefore, it is important to explore sev-
eral databases to achieve a comprehensive search. Data provided include the bibliographic citation, with
some resources also displaying the article abstract and even a link to the full-text article. If the abstract
is included, the system is referred to as an abstracting system; if not, the resource is an indexing system.
Interpreting data presented only in abstract form is appealing but almost always inappropriate. A clini-
cal decision should never be made from simply reading an abstract. The corresponding article should be
reviewed and considered in the clinical decision-making process.
It is important to evaluate secondary resources. For example, there is a lag time between the time from arti-
cle publication and the time to indexing into a secondary resource. With PubMed, the article is cataloged,
indexed, and assigned biomedical terms. The indexing information and the article are then uploaded to the
database and provided to the vendors of the database before finally becoming available to the user. The time
involved in this process will vary among secondary resources; the user must keep in mind that a search may
not produce the latest information on the search subject. Some secondary resources (e.g., PubMed) are able
to access in-process records and provide this data.
The cost of secondary resources is typically based on the number of users granted access; therefore, they
often require a library or institutional budget to finance. The ease of use varies among secondary resources.
Each source uses a powerful search engine; these search engines may or may not use the same language,
and there is no standardization of search terms across secondary resources. The user must become familiar
with the structure and terminology of these databases to search effectively. Becoming proficient at search
techniques also requires practice. Table 1 lists common secondary sources.
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Table 1. Common Secondary DI Sources

Source Search Language Comments
MEDLINE MeSH Available through a variety of services:
National Library of Medicine through PubMed
(www.ncbi.nlm.nih.gov/PubMed) (free)
Ovid (www.ovid.com) (commercial); allows search
of more than one database at a time; offers other
databases, such as those for dentistry and alternative
health
EBSCO (www.ebscohost.com); allows search of more
than one database at a time; offers other databases,
such as those for dentistry and alternative health
(commercial)
Excerpta Emtree: Contains more than 7500 titles from mostly peer-
Medica’s Contains 58,000 preferred terms reviewed journals, including 2000 not in MEDLINE
Embase (of which more than 28,000 are drugs Includes 800 conference and 260,000 conference
and chemicals) and more than 240,000 abstracts
synonyms (with over 150,000 drugs and For more information, go to www.embase.com
chemicals)
All MeSH terms are included
Generic names as referenced by the FDA
and European Medicines Agency (EMEA)
IDIS Uses United States Adopted Name Contains more than 200 peer-reviewed English-
(aka IOWA) (USAN) and the International language medical and pharmaceutical journals
Classification of Diseases (ICD) coding Includes data back to 1966
system
Full-text articles available electronically from 1988
Descriptors may differ from MeSH terms to present (articles from 1966 to 1988 on microfiche)
For more information, go to www.uiowa.edu/~idis/
idistday.htm
IPA Descriptors may differ from MeSH terms Contains information from more than 800 pharmacy
and health-related journals published worldwide
since 1970
Available through Ovid and EBSCO
Concentrates on all aspects of drug development,
pharmacy professional meetings, and state pharmacy
journals including meeting abstracts
For more information, go to http://science.thomson-
reuters.com
DI = drug information; FDA = U.S. Food and Drug Administration; IDIS = Iowa Drug Information Service; IPA = International Pharmaceutical
Abstracts; MeSH = Medical Subject Heading.
B. Tertiary DI Resources
Tertiary references often are the starting point to identify information because they typically provide a fairly
complete overview of information on a specific topic. These references are convenient, easy-to-use, and
familiar to most pharmacists. Their most significant limitation is the lag time for publication. Other limita-
tions may include author bias, inaccurate information, or lack of author expertise. Therefore, it is important
for readers to critically evaluate tertiary references. This chapter focuses on the online tertiary resources.
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In evaluating tertiary literature, the important questions to ask include, “What are the qualifications of
the evaluating author(s) and/or editor(s)?”, “What is the timeliness of the information?”, “Are the citations
appropriate?”, and “Is the publication free from potential bias?” Content should be considered as well. Some
references have a general scope of coverage and others are more detailed, providing a specific focus on a
topic. For tertiary references that provide a DI focus, the user should consider the type of drugs included in
the reference (e.g., prescription only, over-the-counter, herbals) as well as the drug’s country of origin.
The types of information reported should also be considered (e.g., U.S. Food and Drug Administration
[FDA]-approved uses only or off-label uses as well). Organization of content is also an important. Several
tertiary references provide excellent tables and figures that are easy to use and organize content in a concise
manner. Users will often come to prefer one reference over another based on the organization of the infor-
mation such as tables, appendices, or special sections. There are hundreds of tertiary references available
and no pharmacy practice setting will provide access to them all. Hospitals, community pharmacies, clinics,
and other practice settings will select references based on their particular needs, funding, patient popula-
tions, and the types of information commonly required.
Specific content titles of commonly used electronic tertiary databases are listed in Table 2. Common fea-
tures of these databases are compared in Table 3.
Table 2. Content of Electronic Tertiary Resources

Clinical
Pharmacology Facts and Comparisons Lexicomp Micromedex
MedCounselor Drug Facts and Comparisons Pediatric Dosage Handbook POISINDEX
Sheets Drug Interaction Facts DI Handbook IDENTIDEX
Drug Identifier Drug Interaction Facts: Herbal Geriatric Dosage Handbook Emergindex
Trissel’s 2 Supplements and Food DI Handbook for Nursing, for DRUG-REAX
MedFacts (patient information in Advanced Practice Nursing, Trissel’s 2
English and Spanish) for Oncology, for Psychiatry, Martindale–The
Comparative Efficacy Content for Anesthesiology & Critical Complete Drug
The Review of Natural Products Care Reference
A to Z Drug Facts Pharmacogenomics Care Notes (formerly
Nonprescription Drug Therapy Handbook USP-DI vol. 2, Advice
Off-Label Drug Facts Series of handbooks for for the Patient)
Trissel’s 2 dentistry REPRORISK
Cancer Chemotherapy Manual AHFS Material Safety Data
5-Minute Clinical Consult King’s Guide to Parenteral Sheets (MSDS)
ToxFacts Toxicology Treatment Admixtures Laboratory Advisor
Guidelines The Orange Book NeoFax
Healthwise Patient Instructions TOXNET (information on Index Nominum
The Formulary Monograph Service toxicology, carcinogenicity,
Martindale – The Complete Drug and drugs in pregnancy and
Reference lactation)
AHFS = American Hospital Formulary Service
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Table 3. Features of Electronic Tertiary Databases

Facts and Comparisons
Clinical Pharmacology eAnswers Lexicomp Micromedex
Drug identification a
Search by NDC number Search by partial or Comprehensive; 23,000
complete NDC number U.S. and foreign drugs
Drug interactionsb Drug-drug, duplications, Drug-drug, drug- Drug-drug, drug- Drug-drug,
drug-food, ethanol, labo- disease, duplications, laboratory, drug-food, duplications, allergy,
ratory, tobacco, caffeine allergy, drug-food, allergy, herbal, drug-food, ethanol,
ethanol, laboratory, pregnancy, OTC laboratory, tobacco,
tobacco, pregnancy, pregnancy, lactation
lactation
IV compatibility Trissel’s 2 Trissel’s 2 King’s Guide to Trissel’s 2
Parenteral Admixtures
Laboratory Chart of normal labora- Chart of normal Pertinent information in Individual laboratory
information tory values laboratory values monographs value monographs
Chart of normal
laboratory values
Patient counseling English and Spanish Drug, oncology-specific Drug, disease, and Drug, disease, and
materials administration, OTC procedural information; procedural; English,
administration 19 languages including Spanish, and 13 other
techniques, disease- English and Spanish languages; customizable
focused; English and
Spanish
Inert ingredients Located in how supplied Located under product Not readily available Through Tox and Drug
section list Product Lookup
Teratogenicity Pertinent information in Uses Briggs’ Drugs in Through TOXNET, Through REPRORISK
information monographs Pregnancy and Lactation Hazardous Substance
database
Breastfeeding Pertinent information in Uses Briggs’ Drugs in Through TOXNET, Through REPRORISK
information monographs Pregnancy and Lactation LactMed
Investigational drug Yes, readily referenced Limited information Limited Yes, readily referenced
monographs
CAM information Yes Through review of Through Natural Yes; AltMedDex
Natural Products Products database
FDA recalls No Weekly FDA news Link to FDA No
thread
Drug shortages No Weekly FDA news Link to ASHP No
thread
MSDS No No No Yes
Referencing Comprehensive Limited Limited Extensive
Available platforms Web-based, PDA Web-based, PDA, print Web-based, PDA, print Web-based, PDA
Costc Subscription required; Subscription required Subscription required Subscription required.
30-day free trial for basic and advanced for individual compo- Various package prices
available; free access to packages nents; package prices available
students available
a
Search solid dosage forms by color, shape, imprint, scoring; image available.
b
Information provided within individual monographs.
c
Subscriptions available to educational institutions free or at a nominal charge.
CAM = complementary and alternative medicine; FDA = U.S. Food and Drug Administration; IV = intravenous; MSDS = Material Safety Data
Sheets; NDC = National Drug Code; OTC = over-the-counter; PDA = personal digital assistant.
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1. Clinical Pharmacology
This database offers a product comparison tool that can retrieve a list of products for a selected allergy
or dietary restriction criteria (e.g., sugar free, alcohol free, latex free, sodium free, dye free). Most infor-
mation is readily referenced with a link to PubMed citations, although some information, such as the
adverse event reporting, is not referenced. Clinical Pharmacology also offers a drug comparison tool
that easily generates information on product dosage forms, clinical attributes, and adverse events.
2. Facts and Comparisons eAnswers
Facts and Comparisons eAnswers is the online version of the Facts & Comparisons textbook. Abbreviated
DI is referenced, although not extensively. One great feature of this database is the comparison charts.
A daily news update that includes FDA recalls is also a standard feature. Additionally, information on
patient assistance programs, look-alike and sound-alike drugs, and a manufacturer index is provided.
3. Lexicomp
Lexicomp is a point-of-service database providing comprehensive DI with over 1700 drug monographs.
As of June 2011, Wolters Kluwer is acquiring Lexicomp to add these clinical references to their other
holdings, including UpToDate. Other information found in Lexicomp includes current drug shortages,
FDA recalls, dangerous drug abbreviations, therapeutically equivalent generic drugs (through the
Orange Book, available at www.accessdata.fda.gov/scripts/cder/ob/default.cfm), and extemporaneous
preparations (through the Pediatric Dosage Handbook found online in the Lexicomp series). References
are not provided for all information; some references provided are not easily retrievable. Lexicomp is a
good source to use when quick retrieval of easy-to-understand data is needed.
4. Micromedex
Micromedex is a tertiary resource designed to provide information to the health care professional about
clinical inquires. This resource, commonly used in the hospital or academic setting, provides a vari-
ety of information in the areas of DI, poison information, acute care medicine, and patient education.
Information is provided as full-text and is referenced throughout.
The DI is divided into two main sections: DRUGDEX and DrugPoints. DRUGDEX is a general tertiary
resource. DrugPoint Summary (formerly known as USP-DI volume I) provides summary information
on dosing, drug interactions, adverse effects, pregnancy warnings, indications, cautions, therapeutic
classes, brand information. DRUGDEX provides evidence-based detailed DI that is gathered from pri-
mary literature and summarized by editorial specialists. Although Micromedex is a large database, the
primary literature is readily referenced and easy to access. Therapeutic indications are given a graded
evidence rating with usage recommendations. For the clinician, Micromedex offers comprehensive,
easy-to-read, extensively referenced data on drugs. Micromedex now offers a drug interaction app
through iTunes that allows an HCP to simultaneously enter 50 medications from a patient profile and
search for interactions.
5. MD Consult/First Consult
MD Consult is a large database that provides comprehensive medical information. MD Consult includes
weekly summaries of journal articles, full-text reference books, practice guidelines, DI (through Gold
Standard), information on what patients are reading in general literature, drug updates, daily medical
news, customizable patient handouts, case of the week practice modules, medical images, clinical topic
tours, and continuing education. First Consult, a part of MD Consult, provides information on over
700 medical topics as well as differential diagnoses and procedures. First Consult also offers an iPhone
app that makes clinical medical information available for personal digital assistants (PDAs) and smart
phones. Of note, MD Consult provides article summaries of top current interest journals as well as a
really simple syndication (RSS) feed.
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6. UpToDate
UpToDate is an evidence-based, peer-reviewed reference that is available through the Web or by PDA.
Content is generated by medical experts in their field and covers more than 16 different medical disci-
plines and 8300 topics. This database is geared toward prescribers, and all information includes sum-
mary documents of evidence-based medicine. UpToDate uses Lexicomp information as the source of
point-of-service DI.
7. Electronic Textbook Databases
There are numerous eTextbook collections available for purchase. These databases contain online text-
books in an electronic format. Large publishers such as McGraw-Hill and Wiley InterScience offer
collections of their books in electronic format. These collections are often geared toward a specific
subject area (e.g., pharmacy, medicine, nursing). Purchasing collections can be more cost effective than
buying individual titles. An advantage of electronic texts is the availability for content to be updated in
a timely fashion. A major disadvantage of these resources is their cost. The contents of two commonly
used electronic textbook databases are listed in Box 1.
Box 1. Contents of Electronic Textbook Sources
AccessPharmacy
This multimedia database has 25 online textbooks. Case studies, laboratory tests, calculators, videos, and effec-
tiveness statements are also available. Titles include Pharmacotherapy: A Pathophysiologic Approach, Goodman
& Gilman’s: The Pharmacological Basis of Therapeutics, Harrison’s Principles of Internal Medicine, Drug
Information: A Guide for Pharmacists, and Goldfrank’s Toxicologic Emergencies. AccessPharmacy offers a
review for the NAPLEX, Multistate Pharmacy Jurisprudence Examination (MPJE), and Top 200 drugs as well as
patient cases. Searching may be done by keyword, curricular topic, or organ system.
STAT!Ref
STAT!Ref contains full-text versions of medical and pharmacy texts including AHFS, Mosby’s Drug Consult,
Rudolph’s Pediatric, Basic and Clinical Pharmacolo-gy, and Stedman’s Medical Dictionary. Subscription rates are
à la carte or by col-lection. Collections are available for dentistry, mental health, nutrition and dietetics, pharma-
cology, and public health. Searching across all texts is available. In addition to popular texts, STAT!Ref offers a
medical newsfeed as well as evidence alert feeds.
AHFS = American Hospital Formulary Service
8. Resources for Handheld Devices

Many tertiary resources have applications for handheld devices like smart phones. All of these applica-
tions contain basic DI such as drug monographs, disease information, and drug interactions; however,
they differ in cost and additional features such as drug identification, calculators, and laboratory infor-
mation. For a list of features available for these electronic resources, see Table 3.
C. Web-Based Resources
Qualified HCPs should be involved in establishing and reviewing sites. The pharmacist cannot control
whether a consumer goes to the Internet for information but can provide patients with tools to help them
glean high-quality information. Table 4 lists questions that a consumer should consider when searching for
credible drug and health information. The pharmacist may also direct the consumer to the NLM video.
Some Web sites have risk calculators for health and wellness (e.g., americanheart.org, mayoclinic.org,
healthstatus.com). These sites may require personal information but usually do not request sensitive iden-
tification information such as Social Security numbers. These sites usually ask the user to set up a secure
account and provide a privacy notice. Personal information should not be given to a site that does not have
a privacy policy or when site security is in doubt.
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Patients and HCPs alike should beware of sites that are blogs, micro blogs, social networks, social book-
marking sites, or collaborative harvesters. These sites are not usually high quality or valid providers of
health and DI. To evaluate these sites, it is important to ask the questions found in Box 1. In general, sites
that end in .gov, .edu, and .org may be more reliable; however, even these should be held to the same criteria
as other sites. This continues to be an important area in which the pharmacist or other HCP can guide the
health-care consumer.
Table 4. Questions Consumers Should Ask About Web-Based DI

Parameter Questions
Source of What or who is the organization/person responsible for the site? Can you readily find this informa-
information tion on the Web site?
Why has the organization/person created the site? What is the mission in providing this service?
Cost of access Does the site want anything from you in return? If so, what and why is that necessary for gaining
access to the information? Does the site want your personal information, and if it does, what will it
do with that information?
Who is paying or funding the site? Is there a site sponsor? Is the sponsorship readily available on the
Web site and openly displayed for the public? Does the sponsor gain any benefit from your reading or
accessing the site?
Quality of Is the information written and/or reviewed by health care experts with proven credentials?
information Where did the information on the site come from? Is it expert opinion, or is it based on studies—
preferably studies that have high-quality evidence or at least studies that have been published in
reputable journals (this can be difficult for consumers to ascertain and may require help from
professionals)? What is the editorial policy of the site?
Is the information current? When was the information last updated with new science?
Usability Does the Web site provide information such as a site map, contact information, a mission/purpose
statement, or the best way to use the site?
Does the Web site make unbelievable claims or claim to be the answer to all questions or prob-
lems? Does it claim to be the only one to have true insight into the issues?
DI = drug information.
Information from the National Library of Medicine (www.nlm.nih.gov).
IV. ACCESSING QUALITY DI RESOURCES
A. Resources for the HCP

The sources of high-quality information for HCP have not changed much in the past 10 years. Most of the
resources are familiar to practitioners and should be relied upon as the better venues for high-quality data.
Studies show that subscription sources provide a faster means to get summarized answers, but these sources
do not always contain all of the necessary primary literature. A study comparing the use of PubMed (a free
resource) versus UpToDate (a subscription source) showed that medical residents spent less time searching
for answers when using UpToDate; however, approximately one-fourth of the queries required additional
searches in PubMedto fully answer the question. Table 5 lists some free-access Internet sites of value for the
HCP interested in providing quality DI.
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Table 5. Available Free Resources for Practitioners

Site Features
PubMed A compilation of more than 21 million articles from the biomedical literature that can be
(www.ncbi.nlm.nih.gov) found in MEDLINE, online books, and life science journals. Many of these articles are
linked to full-text references
Cochrane Library Is more than 28,000 contributors writing systematic reviews dedicated to compiling
(www.thecochranelibrary.com) up-to-date, accurate information about the effects of health care; serves as a leader in
evidence-based medicine
Clinical Evidence An evidence-based medicine database that provides graded levels to help practitioners put
(www.clinicalevidence.com) evidence into practice. The focus is on medical practice in the hospital and in primary care
National Institute for Health An independent organization in the United Kingdom that was started to provide responsible
& Clinical Excellence medical care with evidence-based medicine for promoting good health and preventing and
(www.nice.org.uk) treating ill health
National Cancer Institute Provides unbiased information on the treatment of cancer including clinical trials, cancer
(www.cancer.gov) statistics, research and funding, and patient information
U.S. Food and Drug A government site dedicated to protecting and promoting health by providing information
Administration (FDA) on food, drugs, medical devices, vaccines, blood and biologics, animal and veterinary
(www.fda.gov) products, cosmetics, radiation-emitting products, and tobacco products. Provides both
consumer and professional information. Allows anyone to submit problems identified with
products as well as safety recalls
www.clinicaltrials.gov Includes ongoing federal and privately supported U.S. and international clinical trials
Available for both HCPs and patients
Provides telephone numbers for contacting investigators currently enrolling for clinical
trials
Provides information to potential investigators
www.centerwatch.coma Clinical trial research information for both practitioners and patients
Very patient-friendly; provides several tools including education, publications, and
resources
Offers investigators help in recruiting patients for trials
Web site is extensive, with transparent information, and provides the authors, the purpose,
and history
apps.who.int/trialsearch/ This site is a portal for international clinical trials, but it is not a site for registering clinical
trials. Some countries update their information weekly, whereas others provide monthly
updates. Accuracy of the information depends on the countries submitting
www.controlled-trials.com/ This site allows searching, publishing, and registering of clinical trials. The search engine
used covers seven databases including clinicaltrials.gov, five UK databases, and one
international database. The site also has a journal location service (fee) for accessing
published trials (BioMed Central)
www.cancer.gov/clinicaltrials National Cancer Institute’s search engine for locating more than 8000 cancer trials
Provides patient education about clinical trials as well as recent results from completed
trials
www.clinicalstudyresults.org/ A repository of completed trials, with the results provided in a user-friendly format for
prescribers and patients. Not necessarily presented in a professional format that would
allow drug literature evaluation
Provides manufacturer clinical trial results and can be searched by country, manufacturer,
drug, or disease state/diagnosis
a
Site requires a fee for practitioners but is free to patients.
HCP = health care professional.
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B. Resources for the Patient

The DISCERN tool (www.discern.org.uk/discern_instrument.php) was developed by researchers in the
United Kingdom for patients to use when evaluating sources of information or in evaluating treatment
options. This instrument is the first of its kind to help patients decide between various treatment options
when they are provided with a wealth of or even conflicting information. Other quality resources that could
be recommended to patients are listed in Table 6.
Table 6. Available Free Resources for Consumers

Site Features
DailyMed Provides high-quality information about marketed drugs, including FDA-
(www.dailymed.nlm.nih.gov) approved labeling. Provides consumers with easy-to-read product labeling
Drugs A to Z An easily searched database to look up drugs, both generic and brand
(www.drugs.com/drug_information. name, to find consumer information that can help patients understand their
html) medications including uses, risks, and benefits
Healthfinder Links to 1500 organizations to search for health information that may be
(www.healthfinder.gov) most applicable to a patient. Allows consumers to look at more than one
site for a particular problem
Mayo Clinic High-quality health information written by professionals specifically for
(www.mayoclinic.com/) consumers. Provides a wealth of unbiased information for consumers
MedicineNet.com An online health care publishing company that provides consumers with
(www.medicinenet.com/) easy-to-read but in-depth medical information
MEDLINEPlus Consumer side of the NLM, allowing patients to link to articles and studies
(www.MEDLINEplus.gov) within the government database with user-friendly search terms
Merck Manual: Home Edition for Provides consumers with disease-specific information that is written in
Patients consumer-friendly language
(www.merck.com/mmhe/index.html)
NetWellness A consortium of three medical schools that provide high-quality health
(www.netwellness.org/default.cfm) information and educational services to consumers written by health care
professionals. Allows consumers to meet experts in different fields and ask
them questions
WebMD Provides consumer health–related information written and edited by health
(www.webmd.com) care professionals. Allows users to create health accounts where health
information can be securely scored as well as programs like vaccine track-
ers and food & fitness planners
NLM = National Library of Medicine.
Information from Medical Library Association (http://caphis.mlanet.org/consumer/generalhealth.html).
C. Clinical Trial Data

Current clinical trial data can be a useful tool for clinicians, researchers, and patients, and there are several
resources available online (see Table 5). Clinicaltrials.gov is one of the most useful sites for the U.S. practi-
tioner and has additional resources on international trials as well. Free and relatively easy to search, the site
has clinical trial data that can be extremely valuable for the HCP who works in direct patient care, academia,
or in research. Pharmacists can also find this site helpful when patients ask about ongoing clinical trials.
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D. Evidence-Based Medicine Resources

Evidence-based medicine is a process for making disease management decisions by evaluating and rating
the quality of studies. For the pharmacist, this means combining drug literature evaluation skills with the
knowledge of clinical trial design to determine the usefulness and reliability of clinical trial results. The
HCP can use EBM to decide whether a study has clinical merit that can be translated into patient care, or
if flaws in the study design limit the study’s clinical applicability. Available databases can assist HCPs in
grading the evidence in the literature. However, drug literature evaluation skills are still required for the
decision as to whether the evidence applies to the HCP’s patients and practice site.
As in the use of traditional DI tertiary and secondary databases, it is necessary to search more than one
EBM resource to get a complete picture. The Cochrane Database of Systematic Reviews is a collaboration
of experts who review hundreds of studies about a topic in their specialty. Cochrane strives to include all
known studies, as well as any meta-analyses or systematic reviews. The studies are evaluated using strict
and consistent EBM criteria. The experts then write their own reviews, which are published in the database.
The Cochrane review links all of the published studies that have been provided in the review to the reader.
This allows the reader to look at any of the material on their own as well. Cochrane also notes the date
that the topic was last reviewed as well as any new information. The Cochrane Library has several addi-
tional databases, including the Cochrane Central Register of Controlled Trials (a bibliography of more than
350,000 references to controlled trials) and the Cochrane Methodology Register (more than 9000 references
to the types of research methods).
The Database of Abstracts of Reviews of Effectiveness, which is produced by the U.K.’s National Health
Service, provides access to systematic reviews of the primary literature. Researchers trained in critical
appraisal skills select only the highest quality reviews from published trials, then summarize the results
and published them on the Web site. These reviews include trial outcomes and interventions, trial design
strengths and weaknesses, and implications for clinical practice. Two other U.K. databases of EBM focus
more on economic, social and ethical evaluations; these are the Health Technology Assessments database
(www.inahta.org/HTA/Database/) and the Economic Evaluation Database (www.york.ac.uk/inst/crd/).
The American College of Physicians’ ACP Journal Club evaluates recently published journal articles on
their methodology and clinical relevance to practice. Specialists in the field critically evaluate recent articles,
often pointing out where controversy exists between the study and previously published studies. However,
the Journal Club does not provide a comprehensive EBM review of the other literature available on that
topic.
There are other resources designed to reduce the amount of time the practitioner spends in finding answers
to DI questions. The TRIP database (tripdatabase.com), which is free to clinicians, allows rapid searches
for high-quality EBM articles. The TRIP database includes EBM synopses, EBM systematic reviews, U.S.
published guidelines, core primary research, and extended primary research. The database will send alerts
to a mobile device or e-mail when new information has been added in an area of interest.
UpToDate is a popular subscription service that can provide rapid answers to clinical questions. Described
as a clinical decision support tool to help practitioners at the point-of-care, UpToDate is adding EBM into
the database so clinicians can judge the level of evidence before implementing care. One study reported that
physicians are able to retrieve information faster when using a service like UpToDate compared to database
searches such as MEDLINE or PubMed. However, the study did point out that at least one-fifth of the physi-
cians needed to search PubMed after looking up information in UpToDate to retrieve the primary literature
before implementing therapy.
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E. Clinical Practice Guideline Resources

As clinical practice guidelines (CPG) increase in both quality and quantity, it becomes more difficult to
keep up on the latest guidelines. Table 7 lists some common resources to consider when looking for clinical
guidelines.
Table 7. Resources for Locating Clinical Practice Guidelines

Site Features
Guideline.gov A national guideline clearinghouse of evidence-based guidelines. Has a large
(www.guideline.gov) database of different guidelines from many professional organizations. Provides
expert commentaries, guideline synthesis, guideline resources, annotated
bibliographies, and comparative analysis of guidelines. Site is part of AHRQ
(Agency for Healthcare Research and Quality)
National Institutes of Health Provides guidelines related to cardiovascular, pulmonary, and blood health.
(www.nhlbi.nih.gov) Provides interactive tools and resources. Provides current guidelines and
reports as well as guidelines in progress. Also archives older guidelines for
historical purposes
American College of Physicians Provides current clinical guidelines as part of the American College of
(www.acponline.org/ Physicians Web site. This is a clearinghouse of clinically relevant guidelines
clinical_information/
guidelines/)
Open Clinical An international organization that has created a Web site to promote clinical
(www.openclinical.org/ decision support tools, clinical workflow, and advanced knowledge manage-
guidelines.html) ment technologies within patient care as well as clinical research. Provides
tools and techniques for creating health care applications to improve quality,
safety, and ethical standards
V. SPECIFIC DI RESOURCES
A. Resources on Complementary and Alternative Medicine

The field of complementary and alternative medicine (CAM) continues to expand. The standard references
within this area of DI have not really changed over the years, but publishers continue to improve both the
quantity and quality of the available information. A large number of newer Web-based resources are avail-
able (Table 8). It is difficult to keep up with all of the new products that come to the market from sources in
the United States and around the world. These international references, which are available on the Web, may
be a good way to identify new products that cannot be found in other references. The FDA Web site contains
valuable information on product recalls or products that contain undeclared ingredients.
Standard resources for DI on natural/herbal products include the Natural Medicines Comprehensive
Database (www.naturaldatabase.com), which provides a summary with an indicator of overall safety
and efficacy for each product. Searching both brand and common names is easy, and references for the
product information are provided. Furthermore, this reference indicates whether a specific product is
U.S. Pharmacopeia (USP)-verified, an indicator of quality ingredients. The Natural Standard (www.natural
standard.com), which provides monographs with summary tables of published literature, is a comprehen-
sive source of graded evidence-based natural product information. The monographs also provide dosing and
drug interaction information that can aid in the decision to use a natural product.
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An optimal strategy is to consult multiple sources when evaluating the potential for herbal-drug inter-
actions. In a pilot study of five patient files, the Natural Medicine Comprehensive Database and Natural
Standard Database were compared in the ability to identify potential drug interactions between prescription
medications and herbal therapies. The 21 different drugs in the files resulted in 2522 potential natural prod-
uct and prescription medication drug interactions. However, each database was able to detect only about
50% of the potential interactions. There was also variability in the information provided, with only 205 of
the interactions appearing in both databases.
The Review of Natural Products provides monographs for a large number of herbal products. Known for
its very complete chemistry, pharmacology, and toxicology sections, this resource also references articles,
including both human and animal studies. The Physician’s Desk Reference for Herbal Medicines is useful
for herbal products but does not offer information on other types of CAM. Each product is described in a
monograph followed by references. This resource, which has information similar to those above, is often
packaged with other Thomson DI publications.
Table 8. Select CAM Databases Available in English

Name (Web address) Topic Area Content
Sites with free access
Acubriefs (www.acubriefs.com) Acupuncture 24,000 citations
CAMbase (www.cambase.de) CAM 80,000 citations
CAM on PubMed (www.nlm.nih.gov/nccam/camonPubMed.html) CAM 462,000
Camlis (www.cam.nhs.uk) CAM EBM publications
Cards (http://ods.od.nih.gov/research/cards_database.aspx) Dietary supplements Research projects
Cochrane Collaboration CM Field (www.compmed.umm.edu/ CAM EBM CAM reviews
cochrane.asp)
Datadiwan (www.datadiwan.de) CAM 6000 citations
Extract Database (www.plant-medicine.com/grades/extract/ Acupuncture 8000 citations
main-menu.asp)
Hom-Inform (hominform.soutron.com/) Homeopathy 24,000 citations
IBIDS (ods.od.nih.gov/health_information/ibids.aspx) Dietary supplements 760,000 citations
Sites requiring subscription
Amed (www.ovid.com) CAM 227,000 citations
Arrcbase (www.acupuncture.org.uk) Acupuncture 16,000 citations
China National Knowledge Infrastructure Database TCM > 1600 RCTs on
(www.global.cnki.net/) TCM
HomBRex (www.carstens-stiftung.org) Homeopathy > 900 citations
Mantis (www.healthindex.com/start.html) Osteopathy, chiropractic 280,000 citations
Napralert (www.napralert.org/default.aspx) Herbal 150,000 records
TCMLARS (www.cintcm.com/index.htm) TCM 73,000 citations
Wanfang Database (www.wanfangdata.com/medical/intr.asp) TCM 300,000
CAM = complementary and alternative medicine; EBM = evidence-based medicine; RCT = randomized controlled trial; TCM = traditional
Chinese medicine.
Information from Boehm K, Raak C, Vollmart HC, Ostermann T. An overview of 45 published database resources for complementary and
alternative medicine. Health Info Libr J 2010;27:93–105.
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B. Poison/Product Identification Resources

The area of poison/product identification is becoming more important for today’s pharmacotherapy special-
ist. With prescription drug abuse now the third leading cause of drug abuse among teenagers, the pharmacist
is increasingly called upon to help identify potential toxic medications as well as provide poison/toxicology
information. In 2009, the Drug Abuse Warning Network reported that 4.6 million emergency department
visits were drug-related, with 45.1% of these visits linked to misuse or abuse of legal and illegal drugs. In
2011, the White House Office of National Drug Control Policy reported that prescription drug abuse had
doubled the number of persons visiting the emergency department in the past 5 years, and for the third year
in a row prescription drug abuse surpassed illegal drug abuse. Therefore, it is imperative that the pharmacist
be familiar with standard DI resources on overdose, poisoning, and toxicology.
An excellent resource for reviewing basic toxicology is Casarett & Doull’s Toxicology: The Basic Science of
Poisons. One of the most extensive references on the toxicologic effects of poisons and drugs, this textbook
goes into great detail on the toxicity that occurs within every organ system and also discusses developmen-
tal toxicology, environmental toxicology, food toxicology, forensic toxicology, and occupational toxicology.
Although it is not a good review for acute poisoning from prescription drug abuse, this text is valuable as a
reference in the area of chronic exposure.
Another classic toxicology reference, Goldfrank’s Toxicologic Emergencies, is written in a case study for-
mat. In-depth chapters provide information on various aspects of poisonings. A pocket-sized companion,
Goldfrank’s Manual of Toxicologic Emergencies, describes how to assess the patient and determine the best
treatment option. The manual is a good resource for the pharmacist who might be called upon to provide
clinical treatment recommendations for specific poisonings, or for the pharmacist in the emergency room or
critical care areas who wants to improve their clinical poisoning knowledge base.
The Medical Toxicology Review: Pearls of Wisdom is an excellent and concise review of many drug-related
overdoses. The book is organized in alphabetical order by the drug name or poisoning agent and provides
concise bullet points that are critical for understanding the nature of the poisoning. Medical Toxicology is
a clinically relevant reference that outlines the diagnosis and management of poisonings including those
involving drugs. This textbook provides information on treating a patient with poisoning symptoms from
an unknown cause. Because it also describes the toxicology of biological and chemical weapons, it is a good
source of bioterrorism information for pharmacists.
Drug identification tools are a critical aspect of poisonings or drug abuse management. A number of well-
known databases and textbooks can help the pharmacist, especially if the imprint codes are readily avail-
able. Micromedex with INDENTIDEX, mentioned previously, continues to be a gold standard in the area of
poison and pill identification. Lexicomp provides imprint codes as well as tablet identification features with
pictures. Clinical Pharmacology and Facts and Comparison’s eFacts are other resources that have a tablet
identification feature.
C. Adverse Drug Reactions/Pharmacovigilance Resources

1. New FDA Initiatives
The FDA has recognized that voluntary post-marketing evaluations of drug safety data have not been
the most comprehensive method to identify serious adverse drug reactions. Recent drug-related adverse
events such as spontaneous fractures with bisphosphonates and maternal heart problems in women tak-
ing terbutaline for preterm labor are two prime examples of the insufficiency of the voluntary reporting
system. The FDA has developed new pharmacovigilance methods to improve the spontaneous report-
ing system (MedWatch program), and is working with private companies and academic researchers to
develop and apply these newer monitoring and reporting techniques.
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The FDA is using data mining as a new approach to more rapid identification of potential problems.
Data mining is a statistical process that attempts to find an event, related to a drug, that is occurring
at a higher-than-normal rate within the general population. Signal detection is the process of finding a
higher-than-expected event rate. The FDA uses statistics and both Bayesian and non-Bayesian meth-
ods to identify these signals, then responds with an expert clinical review to determine if there is any
validation to the signal. This data mining allows the FDA to look at multiple or unusual occurrences
in a more timely fashion to see if further research or investigation is necessary. The FDA also offers
an e-mail delivery service to send safety alerts to HCPs. Practitioners can subscribe to the MedWatch
E-List on the FDA Web site. These new FDA initiatives are an important advance in the area of DI
within the last few years. These changes make the FDA Web site a valuable resource in assessing early
adverse reactions and drug interactions. Pharmacotherapy specialists should include this Web site in
their routine surveillance of DI resources.
Under authority granted by the 2007 Food and Drug Administration Amendments Act, the FDA devel-
oped a required Risk Evaluation and Mitigation Strategy (REMS) for manufacturers. This program
aims to ensure that the benefits of a drug or biological product outweigh the potential risks when
the FDA deems that a product may have a risk profile that requires additional limitations. The man-
ufacturer is required to put certain elements in place for the product; these can include a medica-
tion guide, elements to ensure safe use, implementation system, and a communication plan. The FDA
Web site lists the REMS approvals, as well as instructions and guidance for manufacturers devel-
oping the required documents. The draft REMS guidance was posted in February 2011 (www.fda.
gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM244570.pdf);
for pharmacists, a Web site is available listing the REMS drugs (www.fda.gov/Drugs/DrugSafety/
PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm). The REMS program is
so new that there has not been time to determine how helpful these guides will be to the pharmacother-
apy specialist. Ongoing studies are assessing the impact of this program on drug use and safety.
Another area of concern is the boxed warning sometimes required by the FDA because of safety issues.
Several secondary and tertiary references include these boxed warnings on package labeling as required
by the FDA. A 2010 study looked specifically at the boxed warnings as listed in the drug interaction
databases of Facts & Comparisons 4.0, MICROMEDEX DRUG-REAX, and Lexi-Interact. The study
involved 11 drugs with boxed warnings related to contraindicated drug combinations. The authors con-
cluded that additional studies need to be done to explore inconsistencies and suggest clinicians refer to
multiple drug resources when evaluating the possibility of a serious drug-drug interaction.
In 2009, another study looked at five online resources and three online databases to evaluate their doc-
umentation of boxed warnings. The study showed that of the 416 marketed prescription drugs required
to carry a boxed warning, only 135 (32%) were cited as such in all eight resources. Some resources
provided information consistent with the boxed warning whereas others did not identify it as an inter-
action. The researchers indicated that the current registry of boxed warnings is lacking, which means
that clinicians must check multiple sources to verify this type of information. The authors suggest that
clinicians should subscribe to the MedWatch safety alerts that are sent to an HCP’s e-mail account.
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2. Adverse Drug Reaction Resources

In researching adverse drug reactions (ADRs), most practitioners will use the standard tertiary ref-
erences (e.g., MICROMEDEX, Lexicomp, Facts & Comparisons, Clinical Pharmacology). However,
some other textbooks and databases are excellent resources in evaluating and searching for specific
ADRs. One reference that critically reviews the international literature is Meyler’s Side Effects of
Drugs, which provides information on reported ADRs and their management. Side Effects of Drugs
Annual: A Worldwide Yearly Survey of New Data and Trends in Adverse Reactions (www.elsevier.
com) is another review of ADRs that is updated annually. A secondary source of ADR information is
the database Reactions Weekly (www.adisonline.com); this publication is updated weekly and is the
most current ADR information available with minimal lag time. Reactions Weekly provides reports
from journals, scientific meetings, press releases, news from regulatory agencies, and information from
more than 80 World Health Organization International Drug Monitoring Programme participants. In
addition to case reports, Reactions Weekly includes labeling changes, drug withdrawals caused by
safety concerns, ADR research, and current issues in drug safety.
Conclusion
Drug information and drug literature evaluation skills are vital for the pharmacotherapy specialist. Pharmacists
can take the lead in providing DI to other HCPs and to patients and their families. The field of DI continues to
evolve with new and better references, new applications for electronic devices, and new sources on the Internet.
The pharmacist’s skills in drug literature evaluation and EBM are even more important today given the breadth
of information overload. Pharmacists should acquire techniques to find high-quality information to maximize
patient care.
Knowing all the various resources available to both HCPs and the public allows the pharmacist to suggest qual-
ity sources of information. Good drug literature evaluation skills can be a necessary filter to ensure that EBM
is being disseminated. Pharmacists can use their DI skills to participate in developing practice guidelines and
monographs as part of the patient care team. They can also serve in the role of verifying information from cred-
ible sources and advising the team when information may be of poor quality or from references that do not meet
acceptable standards. Pharmacists must rely on the best practices related to DI to benefit patients and HCPs and
ensure high-quality services.
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REFERENCES
1. Boehm K, Raak C, Vollmart HC, Ostermann T. An 12. Thiele RH, Poiro NC, Scalzo DC, Nemergut EC.
overview of 45 published database resources for Speed, accuracy, and confidence in Google, Ovid,
complementary and alternative medicine. Health PubMed, and UpToDate: results of a randomized
Info and Libr J 2010;27:93–105. trial. Postgrad Med J 2010;86:459–65.
2. Clauson KA, Marsh WA, Polen HH, Seamon MJ, 13. UpToDate (www.uptodate.com), accessed January
Ortiz BI. Clinical decision support tools: analysis 4, 2011.
of online DI databases. BMC Med Inform Decis 14.
Bonis PA, Picken GT, Rind DM, Foster DA.
Mak 2007;7:7. Association of clinical knowledge support system
3. Vitry AI. Comparative assessment of four drug with improved patient safety, reduced complica-
interaction compendia. Br J Clin Pharmacol tions and shorter length of stay among Medicare
2006;63:709–14. beneficiaries in acute care hospitals in the United
4. Kupferberg N, Hartel LJ, Prior JA. Evaluation of States. Int J Med Inform 2008;77:745–53.
five full-text drug databases by pharmacy students, 15. Patel MR, Schardt CM, Sanders LL, Keitz SA.
faculty, and librarians: do the groups agree? J Med Randomized trial for answers to clinical questions:
Libr Assoc 2004;91:66–71. evaluating a pre-appraised versus a MEDLINE
5. Raschke CG, Hatton RC, Weaver SJ, Belgado BS. search protocol. J Med Libr Assoc 2006;94:382–6.
Evaluation of electronic databases used to iden- 16. Jacso P. The pros and cons of computing the h-in-
tify solid dosage forms. Am J Health-Syst Pharm dex using Google Scholar. Online Information
2003;60:1735–40. Review 2008;32:437–52.
6. Smith WD, Karpinski JP, Timpe EM, Hatton RC. 17. Shariff SZ, Cuerden MS, Haynes RB, McKibbon
Evaluation of seven intravenous drug compati- KA, Wilczynski NL, Iansavichs AV, et al.
bility references by using requests from a drug Evaluating the impact of MEDLINE filters on
information center. Am J Health-Syst Pharm evidence retrieval: study protocol. Implement Sci
2009;66:1369–75. 2010;5:58–68.
7. Clauson KA, Polen HH, Marsh WA. Clinical deci- 18. Boehm K, Raak C, Vollmart HC, Ostermann T. An
sion support tools: performance of personal digital overview of 45 published database resources for
assistant versus online drug information databases. complementary and alternative medicine. Health
Pharmacotherapy 2007; 27(12):1651-1658. Info and Libr J 2010;27:93–105.
8. Jellinek SP, Cohen V, Stansfield L, Likourezos A, 19. C
heng CM, Guglielmo BJ, Maselli J, Auerbach
Sable KN. A survey of drug information references AD. Coverage of FDA medication boxed warnings
emergency medicine clinicians utilize for pre- in commonly used drug information resources (let-
scribing in pregnant patients. Ann Pharmacother ter to the editor). Arch Intern Med 2010;170:831–3.
2010;44:456–61. 20. Wang LM, Wong M, Lightwood JM, Cheng CM.
9. Polen HH, Zapantis A, Clauson KA, Jebrock J, Boxed warning contraindicated comedications:
Paris M. Ability of online drug databases to assist concordance among three major drug interac-
in clinical decision-making with infectious disease tion screening programs. Ann Pharmacother
therapies. BMJ Infect Dis 2008;8:153. 2010;44:28–34.
10. Kostka-Rokosz MD, McCloskey WM. Survey of
pharmacy preceptors’ use of hand-held electronic
devices. J Am Pharm Assoc 2009;49:69–72.
11. Goodyear-Smith F, Kerse N, Warren J. Evaluation
of eTextbooks: DynaMed, MD Consult and
UpToDate. AFP 2008;37:878–82.
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ANSWERS AND EXPLANATIONS TO SELF-ASSESSMENT QUESTIONS
1. Answer: B in which Human subjects were tested. To limit to only

IPA is the best answer because it contains information clinical trials (Answer D) could result in selection of
specific to pharmacy as well as information presented animal data.
at a pharmacy scientific meeting. Since this question
requires information specific to an IV pump, the best 6. Answer: B
source would be one that contains information spe- Answer B is correct because the FDA Web site is
cific to pharmacy. Ovid (Answer D) is a platform for going to have the most current ADR information that
MEDLINE (Answer C) which contains primary medi- is either being reported by manufacturers or is detected
cal literature. IOWA also contains information regard- via the pharmacovigilance program. The FDA site
ing the primary medical literature. is a good site as a clinician to have e-mail alerts sent
when new ADRs are reported. http://www.fda.gov/
2. Answer: A Drugs/DrugSafety/ucm245011.htm Answer A, www.
MEDLINE, in-process is the best answer because this clinicaltrials.gov, is not the best answer because usu-
source contains those records that are not yet indexed ally these ADRs are not reported through a clinical
with Medical Subject Heading (MeSH) terms. Since the trial. Although clinicaltrials.gov does have safety tri-
pharmacist has not heard of the drug and the physician als and this would be a good source to look at later in
states the drug is new, one can assume that any infor- your searching strategy but it is incorrect because it is
mation contained in MEDLINE is new. IDIS, PubMed not considered a first-line resource for this question.
and IPA do not publish in-process papers and posts For the PPIs and magnesium, there are case series and
papers once publication occurs. observational studies published in the literature start-
ing in 2006 so a Medline search would show results but
3. Answer: C none were clinical trials and a search of clinicaltrials.
The best step to take to limit erroneous data is to limit gov through June 2011 results no trials found. Answer
the sex to female. This would limit the MeSH for aspi- C, www.mayoclinic.com, is incorrect because this site
rin AND stroke to only those studies that included is meant for health care consumers versus information
females. Using the subheading “therapeutic use” for the health care professional. Answer D, www.clin-
(Answer B) would not limit the data as much as restrict- icalevidence.com, would be incorrect because clinica-
ing the search to the female gender since the question levidence.com provides guidelines and does not have
was specific to information in women. A restriction to cutting edge safety data on the site.
publication type of “review” (Answer D) may limit the
search too much and cause one to miss pertinent arti- 7. Answer: B
cles. Using a keyword search provides too many hits Clinicaltrials.gov will provide the best resource to find
that are irrelevant and is not time efficient (Answer A) clinical trials in the area of multiple sclerosis that might
be available in the United States due to this patients
4. Answer: A travel and medical expenses. Clinicaltrials.gov does
MobileMicromedex contains all features of the desk cover trials from other countries but it provides a means
top version of Micromedex. The other mobile plat- to search within the United States by city and/or state.
forms for Clinical Pharmacology, Epocrates (Answer It also provides information on what type of patients
B), Epocrates (Answer C), and Lexi-Drugs (Answer D) would be eligible for the trials. If she has failed on
are currently limited and do not contain a specific drug interferons then the patient would be able to identify
interaction tool. those trials that are using interferons and know those
would not be an option. Answer A, WebMD, would be
5. Answer: C incorrect because WebMD is not the best resource to
Restricting the search to Human and English only will find information on investigational trials around the
result in the most efficient search strategy. Articles to country. It is better suited for consumer educational
be reviewed are those written in the English language purposes. Answer C is incorrect because the FDA
2-643
Web site is not the best resource for finding clinical Answer D is incorrect because the observational stud-
trials. Answer D is a choice that could be considered ies did take into consideration the gender of the patients
but is incorrect when compared to clinicaltrials.gov. and controlled for this in the results that were given in
Controlled-trials.com actually contains clinicaltrials. the review.
gov with other international registries. However, this
site is much more complicated and harder to search. 10. Answer: D
It does allow you to just search clinicaltrials.gov as an Answer D is correct because the two studies are very
option. An internet search took 5 times longer to search different in the type of patients and the type of cancers
clinicaltrials.gov compared to search clinicaltrials. that they are evaluating. Therefore, it is difficult to com-
gov through controlled-trials.com. Since this patient is bine this data to determine overall effect of selenium
looking for trials in the United States then clinicaltrials. on cancers. This is a concern when completing reviews
gov makes more sense from an efficiency standpoint. such as done by Cochrane as well as when researchers
are looking at combining studies from methodologies
8. Answer: A such as meta-analysis. The Cochrane review on sele-
Answer A is correct because providing the RDA for nium points this vary issue out in its limitations related
selenium each day is consistent with the findings from to the methodology. Answer A is incorrect because in
the Cochrane review. The data suggests that there is these two studies the dose of selenium was the same
no benefit when exceeding the RDA especially when even though the SELECT study had a second group
patients are taking doses that exceed 200 mcg/ per that received vitamin E. Answer B is incorrect because
day which is why Answers B and C would be incor- the difference in sample size is not a major factor in
rect. Based on the evidence from Cochrane and the this type of review. Sample size differences can present
SELECT trial, one could argue that this level of supple- challenges with other types of studies. The key is not
mentation of selenium is putting them at an increased so much the sample size difference but rather whether
risk. Lippman SM, Klein EA, Goodman PJ, Lucia MS, the outcome variables were powered. The powering of
Thompson IM, Ford LG, et al. Effect of selenium and the outcome variable is critically no matter the sample
vitamin E on risk of prostate cancer and other cancers: size. Answer C is incorrect because both of these trials
the Selenium and Vitamin E Cancer Prevention Trial were published and the Cochrane review was unable to
(SELECT). JAMA 2009;301(1):39-51. detect any publication bias from studies that had been
Answer D is incorrect because the data does not sug- completed but not reported. Both the SELECT and the
gest that selenium has to be completely removed when NPCT have had multiple publications with both study
it is given at the RDA levels. design and substudy results.
9. Answer: B 11. Answer: A

Answer B is correct because RCTs are a stronger study Answer A is the best answer because this Cochrane
methodology and are usually considered to be better Review was published in May 2011 and stated in the
evidence or higher quality evidence when compared review that the studies were up-to-date through April
to observational study designs. So when evidence is 5, 2011. The student would know to search the litera-
conflicting between RCTs and observational studies, ture from that point on. PubMed offers the best choice
the conclusions from a well-designed RCT are usually to look for the most recent studies since it offers the in
considered superior. An OR is an estimate of relative process feature as it adds studies and publications to
risk but relative risk is still a measure from an obser- the database(. http://www.ncbi.nlm.nih.gov/pubmed/).
vational cohort study design and is still not considered Answer B is incorrect because UpToDate would not
superior to a well-designed RCT. So Answer A is not necessarily be updating the system to include recently
the best answer. Answer C is incorrect because this published studies on all topics in the database in a
just describes a problem with the observational data timely fashion. There is no guarantee that this would
which has some truth to it when looking at two of the be updated for selenium with the latest information.
CI within the results. However, this again is the data Answer C is incorrect because Google is not set up
taken from the observational studies and not the RCTs. to search for the latest studies on a topic and it can be
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difficult to search because it does not provide the same 13. Answer: D
searching strategies and limits strategies that PubMed Answer D is correct because it redirects the consumer
offers. Also, Google does not offer an in process option. to look at better sites and also provides them some tools
Answer D is incorrect because the FDA web site is not when searching the Internet for health-related informa-
designed to provide the latest publication on a specific tion. It provides a platform for the pharmacist to inter-
topic especially this type of topic. act with the consumer and help guide them to better
health information. This also allows a dialogue with the
12. Answer: D patient about looking at testimonials and blogs with-
Answer D is correct because www.guideline.gov pro- out appearing too critical of their choice of Web sites.
vides a comprehensive listing of national and even Answer A and B are incorrect because they are more
some local clinical guidelines. This is a difficult subject critical in nature and do not really provide an oppor-
that does not always lend itself to development of qual- tunity for the pharmacist to educate the patient and
ity guidelines and actually presents a difficult search provide them with alternatives. Answer C is incorrect
strategy in answering the questions. However, the best because WebMD may have a good discussion of atrial
starting place is to see what other guidelines have been fibrillation but this does not directly answer the con-
published in this area. Answer A is incorrect because sumer’s question related to the comparison of the drugs
Google does not offer a good way to search guidelines and it does not open a dialogue with the HCP.
in one place. The searching algorithms for Google are
not the most efficient means to search this topic. Google
may provide some additional information later in the
search strategy but is not the best place to start. Answer
B is incorrect because WebMD is a consumer web
site that is not intended to provide guidelines to health
care professionals. Answer C is incorrect because con-
trolled-trials.com is not a good resource for looking for
national guidelines but rather provides a good resource
for identifying controlled clinical trials. It could be con-
sidered later in the search strategy if one was looking
from clinical trials or even economic trials related to
the use of vitamin D. Other databases are available that
provide better searching strategies for economic studies
than controlled-trials.com.
2-645

Drug Information Resources and Literature Retrieval: Karen L. Kier, M.SC., PH.D., BCPS

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Karen L. Kier, M.Sc., Ph.D., BCPS

Miki Goldwire, M.S., Pharm.D.