nlm express drug information resources at the national library of medicine james e. knoben, pharmd,...

NLM EXPRESS

Drug Information Resources at the National Library of Medicine

James E. Knoben, PharmD, MPH

July 9, 2013

Disclaimer

The views expressed in this presentation are those of the presenter and do not necessarily represent,

and should not be attributed to NLM.

Any reference to a particular medication by generic and/or brand name is for illustrative purposes only

and does not represent endorsement of the commercial product.

Learning Objectives

1.State the names and main features of the five NLM electronic resources for drug information.

2.Describe the conceptual development of these databases and information needs that they fulfill.

3.Discuss navigational methods by which information is obtained from these resources.

National Library of Medicine

NLM Reading Room

World’s Largest Medical Library

• 19 million books, journals, manuscripts, audiovisuals

• MEDLINE/PubMed, 22 million journal citations

• PubMed Central, > 2.5 million full text articles

• ClinicalTrials.gov, > 140,000 clinical studies

• Leading global resource for genomic information

Drug Information Databases

•DailyMed

•Drug Information Portal

•LactMed

•LiverTox

•Dietary Supplement Label Database

Database Types

•Bibliographic – A list of literary citations, sources

•Evidence-Based – A systematic, critical review and summarization of literature and/or best clinical practices

•Portal – Multiple resource searching for specific content, and aggregation of results

•Repository [Factual] – Storage of data, documents, and/or images

All involve selection, organization, and search capability.

Drug Information Databases by Type

Database TypeDailyMed Document repositoryDrug Information Portal Search portal

LactMed Evidence-based data collection

LiverTox Evidence-based data collectionCase repository

Dietary Supplement Label Database Document repository

DRUG INFORMATION DATABASES

DailyMed

•DailyMed

•Drug Information Portal

•LactMed

•LiverTox

•Dietary Supplement Label Database

DailyMed

A document repository of

FDA drug labeling (package insert)

and related information in the public domain

http://dailymed.nlm.nih.gov/

http://dailymed.nlm.nih.gov/dailymed/mobile/

DailyMed Initiative

•Health Technology Partnership, 2005

– Food and Drug Administration*

– National Library of Medicine*

– Veterans Health Administration, Dept. of VA*

– Agency for Healthcare Research and Quality

– National Cancer Institute

* Current Partnership

DailyMed Initiative (cont.)

• Coincides with Structured Product Labeling (SPL)

regulations (November, 2005)

• Uses standardized format and terminology

• Uses eXtensible Markup Language (XML):

– Encodes documents in a format that is human and machine

readable; embeds computer tags to denote data sections

• Improves submission, review and archiving process, and

enables searching for specific information

DailyMed Home Page

DailyMed Searching

•Search methods

– Drug name: brand, generic/active ingredient

– Pharmacologic class (FDA)

– National Drug Code

– Limits to human drugs or to animal drugs

DailyMed Features

• Email label information to yourself or others

• Download all labels or pharmacologic indexing

• Access SPL document archives

• Receive update notices about new label postings

• Preview SPL format (for use by label authors)

• Access a solid dose form identification system

• Link to FDA to report an adverse event (MedWatch)

• Mobile version also available

DailyMed Search Results

DailyMed Sample Record Part 1

Sample Record

DailyMed Options

Side Bar that appears with search result

labeling

DailyMed Additional Resources

• With links (and “canned” searches*)– MedWatch– MedlinePlus*– ClinicalTrials.gov*– PubMed*– LactMed*– Medical Dictionary

DailyMed Search PubMed Articles Part 1

Search PubMed Articles

DailyMed Database

• Stats

– Over 50,000 drugs and 25,000 SPLs

– Updated product labels posted within one day after FDA approval or submission to FDA (when no prior approval is needed)

– SPL updates daily

– Increasing percent of new labels each year

DRUG INFORMATION DATABASES

Drug Information Portal

•DailyMed

•Drug Information Portal

•LactMed

•LiverTox

•Dietary Supplement Label Database

Drug Information Portal

A search engine for Web-based drug information

resources in the public domain from NLM

and other Federal agencies

http://druginfo.nlm.nih.gov/

http://druginfo.nlm.nih.gov/m.drugportal/

Resource Selection Criteria

• The proliferation of drug-related Websites requires

objective review to identify credible information.

– Authority – Owner/publisher/sponsor is a respected or

responsible organization with documented expertise

– Content – Information is reliable: accurate, current, unbiased;

substantive (has value); data source is cited

– Design – Good display, ease of use and navigability

– Purpose – The primary purpose is educational and not

commercial; financial support is disclosed (as appropriate)

– Support – Site is consistently available; includes quality links,

contact information, privacy policy, revision date

Drug Information Portal Features

• Covers drugs from clinical trials through FDA approval and marketing

• NLM resources, such as ClinicalTrials.gov, DailyMed

• Outside resources, such as AIDSinfo, Drugs@FDA

• Drugs with official generic name status, such as US Adopted Name, British Approved Name

• Drugs which have categories extracted from the NLM MeSH Pharmacological Action data

Drug Information Portal Home Page

Summary, detailed summary, and additional resources

Search Results - Ibuprofen

Search Results – Ibuprofen (cont.)

Drug Information Portal Search by Category

MeSH Drug Category Descriptions

Drug Information Portal Search Results for Analgesics

Drug Information Portal Resources by Audience/Class 1

Resources by Audience/Class

Drug Information Portal Resources for Health Professionals 1

Resources for Health Professionals

DRUG INFORMATION DATABASES

LactMed

•DailyMed

•Drug Information Portal

•LactMed

•LiverTox

•Dietary Supplement Label Database

LactMed

An evidence-based information resource on drugs

and chemicals to which breastfeeding mothers

may be exposed, and the effects of those agents

on nursing infants and lactation

http://lactmed.nlm.nih.gov/

http://toxnet.nlm.nih.gov/help/lactmedapp.htm

LactMed (cont.)

• Responds to 2005 “urgent call” to action by the Centers for Disease Control and Prevention for accurate, current, and accessible information on medication use during lactation

• Endorsed by the American Academy of Pediatrics [AAP] as “The most comprehensive, up-to-date source of information regarding the safety of maternal medications when the mother is breastfeeding is LactMed… .”

• Supportive of policy positions of the AAP, American Academy of Family Physicians, Healthy People 2010/2020, UNICEF, WHO, and breast feeding advocacy groups

• Is one of the most accessed databases in the TOXNET suite of databases at the National Library of Medicine

Breastfeeding

• Breastfeeding and human milk are the reference normative standards for infant feeding and nutrition

• Recommendation: exclusive breastfeeding for six months, with continuation of breastfeeding for one year or longer [American Academy of Pediatrics]

• Goal: increase breastfeeding to 75% during early infancy [Healthy People 2010]

• Prevalence of breastfeeding is increasing in the US and worldwide

Human Milk

• Human milk is the most complete form of infant nutrition, rich in nutrients and antibodies

• For most infants, particularly premature babies, breast milk is easier to digest than formula

• Human milk helps protect infants against a number of diseases such as otitis media, atopic disease, respiratory and gastrointestinal tract infections

• Provides immunologic and other benefits that may last into childhood, adolescence and adulthood, including reduction in asthma, type 2 diabetes, and obesity rates

Drug Exposure Factors

• Drugs are excreted in breast milk to varying degrees, and environmental chemicals may be possible contaminants

• Drug and chemical exposure has potential risk with respect to nursing infants

• Absent adequate safety information about a drug, the decision is whether to not breastfeed, or breastfeed with uncertainty, or discontinue a medication

• Mothers often discontinue breastfeeding unnecessarily

• Health professionals and mothers have little reliable information, and most information is inaccurate

LactMed Features

• 1,000 drug, herbal, and dietary supplement records

• Data are derived from the world’s scientific literature, and fully referenced to source documents

• Information prepared by a drug information pharmacist, and quality reviewed by pediatric physician specialists

• Other features include PubMed citation links, cross-file searching capability with other TOXNET databases, links to reliable breastfeeding Websites, glossary

• Apps for iPhone/iPod Touch and Android also available

LactMed Home Page

LactMed Information Categories

• Summary of pertinent information regarding recommendations for use of the medication during lactation

• Drug concentrations measured in the breast milk of lactating women

• Drug concentrations measured in breastfed infants

• Adverse effects reported in breastfed infants

• Possible effects of the drug on lactation

• Alternative medications that have similar therapeutic effect that may be used during breastfeeding

Content by Category

LactMed Sample Record 1Summary of UseDrug Levels Maternal and InfantEffects in Breastfed InfantsEffects on LactationAlternate Drugs

Sample Record: Drug Levels

Possible Effects on Lactation

LactMed Sample Record

DRUG INFORMATION DATABASES

LiverTox

•DailyMed

•Drug Information Portal

•LactMed

•LiverTox

•Dietary Supplement Label Database

LiverTox

An international resource of evidence-based

information and clinical case registry on

drug induced liver injury

http://livertox.nih.gov/

LiverTox Description

A database that provides an array of medical

information in one site on the diagnosis, cause,

frequency, patterns, and management

of liver injury attributed to

prescription and nonprescription medications,

herbals, and dietary supplements

An Information Resource

•LiverTox serves as a…

– Clinical resource for clinical pharmacists, general practitioners, specialists and their patients

– Research resource for specialists and investigators in liver disease and toxicology

– Teaching resource and virtual textbook

Medical, Regulatory, Research Interest

• Drug induced liver injury is…– The cause of 5% of new onset acute liver disease

leading to hospitalization– The leading cause of acute liver failure in the United

States (Acetaminophen and Prescription Drugs)*Lee WM. Recent developments in acute liver failure. Best Pract Res Clin Gastroenterol 2012; 26: 3-16.

• FACTOID: 30% fatality rate in drug induced acute liver failure, absent transplantation. Surgery cost:

$250,000+, and $20,000/year for immuno-suppressive drugs.

Medical, Regulatory, Research Interest (cont.)

• Drug induced liver injury is…– The most common reason for failure of new drugs

in clinical trials– Until 2000, the leading cause of medications being

withdrawn from the market (Cardiovascular events now prevail)

• FACTOID: R & D costs are variably estimated to be $100 million to > $1 billion, over 10 years, to bring a new drug to market.

DILI Characteristics

• Can resemble many forms of acute and chronic liver disease, such as acute viral hepatitis, biliary obstruction, chronic hepatitis, fatty liver disease

• A diagnosis of exclusion

• Usually idiosyncratic; varying mechanisms

• Categorized into 12 clinical presentations/phenotypes

• Caused by at least 500 drugs and numerous herbals

Drugs Most Causative of DILI

• Antibiotics (eg, amoxicillin/clavulanate, ciprofloxacin,

minocycline, nitrofurantoin, sulfonamides, telithromycin)

• Anticonvulsants (eg, carbamazepine, phenytoin, valproate)

• Antidepressants/antipsychotics (eg, atomoxetine, bupropion,

duloxetine, olanzepine)

• Antifungals (eg, ketoconazole, terbinafine)

• Antituberculars (eg, isoniazid, pyrazinamide)

• Analgesics (eg, diclofenac, indomethacin, sulindac)

• Rheumatologics (eg, allopurinol, infliximab, interferon beta)

Herbals/Supplements Most Causative of DILI

• A rising proportion of cases are due to herbals and dietary supplements, and mixtures thereof; examples include…– Anabolic steroids

– Chaparral

– Ephedra

– Green tea extracts

– Usnic acid

– Valerian

LiverTox Home Page

LiverTox Drug Search

LiverTox Classes of Drugs Page

LiverTox Components

• Four major components:

Clinical-Diagnostic Overview

Drug Records

Case Report Registry

Information Resources

LiverTox Side Bar – Components

LiverTox – Overview

• Clinical-Diagnostic Overview

– Clinical course and diagnosis

– Phenotypes (clinical signatures)

– Causality assessment

– Severity grading

– Likelihood of drug association

LiverTox Overview: Course, Diagnosis

LiverTox – Drug Records

• Drug Records, including

– Drug/Medication Classes

• Incorporates individual drugs within classes

– Herbals, Dietary Supplements

– Candidate agents include those that…

• Cause definite DILI

• Cause possible DILI

• Lack scientific evidence of DILI

Drug Record Sections

Sections Description

Overview Introduction, background, hepatotoxicity presentation, mechanism, outcome and management

Case Examples From Drug-induced Liver Injury Network, published literature, NIH clinical center

Histology From the national cancer institute and other clinical/scientific sources

Product Information

Molecular formula, chemical structure, trade name(s), product labeling

References From literature, annotated, PubMed link

LiverTox Sample Record 1

Case Report

Histology (Acute Hepatitis)

References

Reference list of books and journals.

Includes hepatologist-written annotations and PubMed citation links.

Product Information

Other Reference Links

LiverTox – Case Report Registry

• Case Report Registry (http://livertox.niddk.nih.gov/)

– Allows the user to submit a clinical case

– Provides structured format for data entry

– Generates printable case summary

– Automated submission to FDA MedWatch

– Cumulative registry allows future analysis (drug use trends, demographics…)

LiverTox Case Report Registry Home Page

LiverTox Case Report Registry Summary Report 1

LiverTox Case Report Registry Summary Report 2

LiverTox – Information Resources

• Information Resources

– Clinical alerts, news, listserv

– Conference proceedings

– Information resources

– Research data from other programs

– Abbreviations, glossary

LiverTox Status

• Livertox Status

– 700 drug records completed, with 15,000 references with annotations

– Goal of 1,000 drug, herbal and supplement records

– Currently gaining a worldwide audience

– Content maintained by NIDDK and other specialists

DRUG INFORMATION DATABASES

Dietary Supplement Label Database

•DailyMed

•Drug Information Portal

•LactMed

•LiverTox

•Dietary Supplement Label Database

Dietary Supplement Label Database

A document repository derived from dietary

supplement product labels, as provided by the

manufacturers, for products marketed in the U.S.

http://dsld.nlm.nih.gov/

Dietary Supplement

• An oral product intended to supplement the diet, containing one or more dietary ingredients, including vitamins, minerals, herbs or other botanicals, amino acids and other substances, or their constituents. The product is not intended to diagnose, treat, cure, or prevent any disease.

• FDA does not preapprove dietary supplement products for safety and effectiveness (unlike drugs); for ingredients sold after 1994, the manufacturer must verify that there is reasonable evidence regarding the safety of its use.

• The product must be properly labeled with specific information: product name, content quantities, mfr. information, directions for use, Supplement Facts panel (eg, serving size, ingredient list, amount per serving by weight, components of blend)

Label Database Background

• A joint project of the Office of Dietary Supplements (ODS) and the National Library of Medicine

• Results from a collaboration that involved representatives from most NIH components and numerous other agencies, such as the FDA, CDC, Agency for Healthcare Research and Quality, Consumer Product Safety Commission, Dept. of Agriculture

• Initial release provides label ingredients on 17,000 products; with regular updates, will eventually include most of the 55,000 dietary supplements in the U.S. market

• Will also serve as a research resource for studies on dietary supplement availability and formulation trends

Label Database Features

• Provides label information for products that are currently on the U.S. market and those discontinued/no longer available on the U.S. market

• Provides complete information from dietary supplement product labels, and images of the product labels

• Provides both quick and advanced search options

• Searchable by ingredient, product name, specific label text, manufacturer or distributor

• Advanced search allows combining search terms

Dietary Supplement Label Database Home Page

Advanced Search

Advanced Search (cont.)

Search Page: Dietary Ingredients

Search Page: Products

Search Page: Contacts

Record: Product Information

Record: Dietary Supplement Facts

Record: Label Statements

Record: Images

Drug Information at NLM

CONTACT INFORMATION

Specialized Information Services, NLM

Toxicology and Environmental Health

Information Program (TEHIP), NLM

tehip@teh.nlm.nih.gov

Thank you!