1. Literature Searching for the IRB Protocol Shannon Potter, MLIS May 10, 2013

2. Financial Disclosure Neither speaker has a financial interest or relationship.

3. 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

4. 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

5. 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 http://www.hhs.gov/ohrp/detrm_letrs/jul01a.pdf

6. 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

7. 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

8. 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

9. 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.

10. 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

11. Types of Literature Meta- Analysis Systematic Review Randomized Controlled Trial Cohort studies Case Control studies Case Series & Case Reports Animal research & Laboratory studies

12. 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

13. Literature Search: Tracking Investigators  Web of Science Searching of the references cited in paper Search for citations to key papers to locate similar research

14. 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

15. How to Access PubMed http://www.mc.vanderbilt.edu/diglib/

16. Full Text Access via PubMed

17. Accessing Full Text Articles  What is the difference between PubMed and PubMed Central (PMC)? PubMedPubMed 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)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.

18. PubMed Features  My NCBI save searches, save collections, receives email alerts  Single Citation Matcher conveniently find and access an article  Limits limit the set of results by language, date or journal subsets  Extensive help and user documentation includes tutorials and handouts

19. 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)

20. 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

21. 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. http://druginfo.nlm.nih.gov/  Micromedex http://www.thomsonhc.com/hcs/librarian provides searchable databases for drug information— toxicology, drug interaction, contraindications, clinical effects, dosing, and other details. http://www.thomsonhc.com/hcs/librarian  FDA MedWatch http://www.fda.gov/medwatch/ provides timely safety information on prescription and OTC medications, as well as nutritional products and medical devices. http://www.fda.gov/medwatch/

22. 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 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.htmlhttp://www.mc.vanderbilt.edu/km/ebm/rics.html

23. QUESTIONS