Literature Searching for the IRB Protocol

Shannon Potter, MLISMay 10, 2013

Financial Disclosure

Neither speaker has a financial interest

or relationship.

Agenda

Why is it important to conduct a literature search for a study protocol How to construct an effective literature search Consulting resources: Databases and Information Sources

Protocol Content

Study Schema 1.0 Background 2.0 Rationale and Specific Aims 3.0 Animal Studies and Previous Human Studies 4.0 Inclusion/Exclusion Criteria 5.0 Enrollment/Randomization 6.0 Study Procedures 7.0 Risks of Investigational Agents/Devices (side effects) 8.0 Reporting of Adverse Events or Unanticipated Problems involving Risk

to Participants or Others 9.0 Study Withdrawal/Discontinuation 10.0 Statistical Considerations 11.0 Privacy/Confidentiality Issues 12.0 Follow-up and Record Retention

Appendices

OHRP Determination Letter

Ellen Roche, a healthy volunteer, died as a result of her participation in a research study at John Hopkins.

OHRP noted “the investigators and the IRB failed to obtain published literature about the known association between hexamethonium and lung toxicity.”

OHRP Determination Letter to John Hopkins is located at: http://www.hhs.gov/ohrp/detrm_letrs/jul01a.pdf

Why do a literature search?

A comprehensive and systematic literature search is the best practice to:

avoid missing important information demonstrate need for proposed research ensure that the research question has not already been answered stay abreast of new research

With respect to the IRB protocol: Missing information can lead to major problems in the approval the

protocol or even compromise the safety of participants Poorly constructed protocol lacking the scientific background information

may not yield useful or replicable results

How does the literature search support the protocol?

Provide background information on a study protocol Cite the incidence or prevalence of a condition or a

disease Summarize the information or lack of information to

support the purpose and relevance of the research question

Identify existing data to support the number of participants needed to demonstrate a difference in a comparative study

Identify the distribution, frequency and types of possible adverse events or effects

Effectively searching the literature

Challenges include: Abundance of information can make it difficult to find the

best, relevant information Searching can be time consuming and frustrating

Why not just use

Sources of Information

Digital Library vs. databases Digital Library is a portal to electronic resources (books, journals,

databases) Databases contain article citations (e.g. PubMed, Web of

Science)

Getting started: background information UpToDate® is a database of synthesized clinical evidence and

practice expertise. Content is based on journal literature to offer current practice recommendations supported by high-quality evidence.

MDConsult is a virtual medical library that includes the full-text of well-known journals and textbooks, clinical guidelines, drug information, and patient education handouts in English and Spanish.

Prepare to ask a useful question and generate an effective query

Identify the context and key concepts Establish limits such as date of

publication or specific journal titles Decide whether the search must be

exhaustive or specific Select appropriate databases and

resources List the all the terms and keywords

Types of Literature

Meta-Analysis

Systematic Review

Randomized Controlled Trial

Cohort studies

Case Control studies

Case Series & Case Reports

Animal research & Laboratory studies

Literature Search: Locating Journal Articles

PubMed (Medline) Key resource for biomedical literature Multiple searching functions

Search using subject headings (MeSH) Combine searches & use keyword searching

(vitamin C OR vitamin e) AND myocardial infarction Print articles

Check abstract link and Digital Library

Literature Search: Tracking Investigators

Web of Science

Searching of the references cited in paper

Search for citations to key papers to locate similar research

National Center for Biotechnology Information (NCBI)

 PubMed

Strengths Provides access to the biomedical journal literature, including over 22 million

citations from the mid-1960's to the present Controlled vocabulary (MeSH) helps to focus your search Provides links to full-text electronic articles Updated daily "Related Articles" feature uses a word-weighted algorithm to link from a particular

citation to additional relevant material

Weaknesses Can be time-consuming to search because of its size Quick searches may omit relevant citations, with the danger that you may miss

important viewpoints in the literature Controlled vocabulary terms (MeSH) are updated annually, so may not

accommodate new concepts well Includes literature from over 70 countries, but has a North American bias and

may omit relevant European literature

How to Access PubMedhttp://www.mc.vanderbilt.edu/diglib/

Full Text Access via PubMed

Accessing Full Text Articles

What is the difference between PubMed and PubMed Central (PMC)?

PubMed is a database that contains over 22 million citations and abstracts of articles from life science, medicine, veterinary medicine, and biotechnology journals. It includes some links to full text articles in PubMed Central and other locations.

PubMed Central (PMC) is the U.S. National Institutes of Health (NIH)free digital archive of biomedical and life sciences journal literature.It includes more than 2 million full-text articles archive that are provided for free to the public. Most articles have a corresponding citation in PubMed. PMC contains additional material, such as book reviews, that are considered out of scope for PubMed.

PubMed Features

My NCBIsave searches, save collections, receives email alerts

Single Citation Matcherconveniently find and access an article

Limitslimit the set of results by language, date or journal subsets

Extensive help and user documentationincludes tutorials and handouts

Example Search Strategies

Complications:

("Mesh heading/complications"[MAJR] OR "Mesh heading/adverse Effects"[MAJR]) OR (“Mesh heading”[MeSH] AND ("Postoperative Complications"[MeSH] OR "Intraoperative Complications"[MeSH] OR “Treatment Outcome”[MeSH]))

The subheading adverse effects includes the following subheadings: /toxicity and poisoning

Therapy:

(“Mesh term” [MeSH] AND “Therapeutics” [MeSH]) OR (“MeSH term/therapy”[MeSH])

Consider including additional facets for specifics types of therapy (e.g. drug, diet, surgery subheadings)

Example Literature Requests

Relative rate of infection for subcutaneous access ports, tunneled catheters, Hickman catheters and PICC lines for long-term venous access

Pharmacokinetics of intravenous lidocaine in normal and pregnant subjects

Databases: PubMed, MICROMEDEX

Searching for Drug Information

NLM/NIH Drug Resource http://druginfo.nlm.nih.gov/

Access drug information from the National Library of Medicine and other government agencies; search by trade or generic name. Includes a link to resources for researchers.

Micromedex http://www.thomsonhc.com/hcs/librarian provides searchable databases for drug information— toxicology, drug interaction, contraindications, clinical effects, dosing, and other details.

FDA MedWatch http://www.fda.gov/medwatch/

provides timely safety information on prescription and OTC medications, as well as nutritional products and medical devices.

Literature Search: Additional Resources

Other useful resources Pharmacology/drug studies: EMBASE (European literature) Biosciences-related or animal studies: BIOSIS, Web of

Science Behavioral/psychology: PsycInfo, Social Sciences Index Nursing: CINAHL Authoritative volume on citing print and electronic medical

information: NLM "Citing Medicine" at the NCBI Bookshelf http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=citmed.TOC&depth=2

For additional assistance, contact the EBL’s Research Informatics Consult Service http://www.mc.vanderbilt.edu/km/ebm/rics.html

QUESTIONS