Upcoming IRB Improvements for AAHRPP and Best Practice 4 th Friday Research Coordinator Lunch & Learn 8/28/09 Monika Markowitz, PhD, MA, RN, MSN Director, Office of Research Compliance and Education Office of the Vice President for Research

Areas to cover: FDA related: Change in PI, IRB registration, retaining data OHRP and NIH Conflict of Interests Reporting Form and Supplement Injury clause in ICF – WIRB and VCU IRB IDP – investigational use of drugs in out-patient setting Genetic research: GWAS & GINA Sampling of WPP enhancements Processes and structure – Electronic submission & IRB Leadership and Enhancement Committee Reminder: CITI Refresher due by end of 2009 for courses taken in 2007 or before

FDA IRB Inspection (6/22-6/24) IRB review of change in PI: Modify WPP VIII-5 Review of Modifications to Research Change may be considered minor if the following criteria apply: a) the individual must have extensive VCU research experience, b) is well- qualified to carry out the research in the designated research role, and c) has other similar types of research projects with the IRB IRB ensures the following are checked if criteria not met: Disqualified/Restricted/ Restrictions Removed/ Assurance Lists for Clinical Investigators suranceList/default.htm FDA Debarment List htm

IRB registration with DHHS New Subpart E - requires all IRBs that review human subjects research conducted or supported by HHS and that are designated under an assurance of compliance approved for federalwide use (i.e, a Federalwide Assurance (FWA)) by OHRP to register with HHS. Effective July 14, 2009 for never registered, September 15, 2009 for changes. Incorporates data for OHRP and FDA Additional information to be provided: - approximate numbers of all active protocols and active protocols involving research conducted or supported by HHS; - approximate number of full-time equivalent positions devoted to the IRB's administrative activities. - approximate number of active protocols involving FDA- regulated products reviewed. For purposes of this rule, an ``active protocol'' is any protocol for which an IRB conducted an initial review or a continuing review at a convened meeting or under an expedited review procedure during the preceding 12 months, and; - description of the types of FDA-regulated products (such as biological products, color additives, food additives, human drugs, or medical devices) involved in the protocols that the IRB reviews.

Retaining Data when Subjects Withdraw from FDA-regulated Research Data Retention When Subjects Withdraw from FDA- Regulated Clinical Trials - Information Sheet Data Retention When Subjects Withdraw from FDA- Regulated Clinical Trials - Information Sheet (10/2008) M pdf M pdf Key Points: For FDA-regulated research, when a subject withdraws from a study, the data collected to the point of withdrawal stays with the study and may not be removed Subject may withdraw from intervention, but may agree to follow-up and data collection. This requires a separate IRB-approved consent form and procedure.

OHRP Quality Improvement Activities FAQ’s - QI vs. Research Question 4: Can I analyze data that are not individually identifiable, such as medication databases stripped of individual patient identifiers, for research purposes without having to apply the HHS protection of human subjects regulations? Answer: Yes. Whether or not these activities are research, they do not involve “human subjects.” Question 6: If I plan to carry out a quality improvement project and publish the results, does the intent to publish make my quality improvement project fit the regulatory definition of research? Answer: No. The intent to publish is an insufficient criterion for determining whether a quality improvement activity involves research.

COMPENSATION FOR INJURY - Proposed language for VCU/WIRB Consent Template Note: This language should be used when Sponsor agrees to pay If you are injured by or become ill from participating in this study, please contact your study doctor immediately. Medical treatment is available at the Virginia Commonwealth University Health System (VCU Health System). Your study doctor will arrange for short-term emergency care at the VCU Health System or for a referral if it is needed. The Sponsor will reimburse you or the VCU Health System for the costs of reasonable and necessary medical care for diagnosis and treatment of a research injury. A research injury is any injury or illness caused by your participation in the Study. If you are injured by a medical treatment or procedure that you would have received even if you weren’t in the study, that is not a research injury. Fees for medical treatment of injuries or illness which are not research injuries may be billed to you or to appropriate third party insurance. Payment for such things as lost wages, expenses other than medical care, or pain and suffering will not be offered. To help avoid injury, it is very important to follow all study directions.

Investigational Drug Pharmacy & Control of Drugs for Research VCU IRB INITIAL REVIEW SUBMISSION FORM 11. Will the VCU/VCUHS INVESTIGATIONAL DRUG PHARMACY (IDP) be utilized (required for all inpatient projects)? Y ES N O * If NO, your research submission must include a descriptive plan regarding appropriate drug storage and dispensing for any investigational drugs or biologicals used in the research. Guidance and the form for describing the management plan is located at Submit the form to the IDP. Upon IDP’s receipt of the plan an automated response is sent back. Include the IDP confirmation AND the completed plan as an attachment. For assistance, please call the I NVESTIGATIONAL D RUG P HARMACY at

Conflict of Interests Reporting and Supplement Form Proposed Clarifications and Rearrangements: … the Principal Investigator and all other VCU investigators… …must report financial interests in any external entity that is related to the work to be conducted under the proposed project or is interested in the results of the project. Move definitions of ‘financial interests’ to the first page Supplement Form – Briefly describe the financial interests and how related to the work…

Genetic Information Nondiscrimination Act (GINA) (April 7, 2009) - Guidance on the Genetic Information Nondiscrimination Act: Implications for Investigators and Institutional Review Boards Intended primarily for investigators who conduct, and institutional review boards (IRBs) that review, non-exempt human subjects research involving genetic testing or collection of genetic information. The guidance document provides background on protections provided by the Genetic Information Nondiscrimination Act of 2008 (GINA) and discusses some of the implications of GINA for investigators who conduct, and IRBs that review, genetic research, particularly with respect to the criteria for IRB approval of research and the requirements for obtaining informed consent under the Department of Health and Human Services regulations for the protection of human subjects (45 CFR part 46).

GINA Protections for IRB consideration BMR ICF template (OHRP language proposed: GINA (45 CFR (a)) Protections for genetic research: [Include this language about the GINA law, see OHRP guidance document at for more information]OHRP guidance document A new Federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it illegal for health insurance companies, group health plans, and most employers to discriminate against you based on your genetic information. This law generally will protect you in the following ways: Health insurance companies and group health plans may not request your genetic information that we get from this research. Health insurance companies and group health plans may not use your genetic information when making decisions regarding your eligibility or premiums.

ICF template continued Employers with 15 or more employees may not use your genetic information that we get from this research when making a decision to hire, promote, or fire you or when setting the terms of your employment. All health insurance companies and group health plans must follow this law by May 21, All employers with 15 or more employees must follow this law as of November 21, Be aware that this new Federal law does not protect you against genetic discrimination by companies that sell life insurance, disability insurance, or long-term care insurance.

Genome-Wide Association Studies (GWAS) What is a genome-wide association study? Involves rapidly scanning markers across the complete sets of DNA, or genomes, of many people to find genetic variations associated with a particular disease. Once new genetic associations are identified, researchers can use the information to develop better strategies to detect, treat and prevent the disease. Such studies are particularly useful in finding genetic variations that contribute to common, complex diseases, such as asthma, cancer, diabetes, heart disease and mental illnesses.

Genome-Wide Association Studies (GWAS) NIH accepts data into the GWAS data repository after receiving certification that IRB has approved submission into GWAS. Certification assures that: Data submission adheres to applicable laws and VCU policies Appropriate research uses and exclusions are delineated Identities of subjects not to be disclosed to GWAS repository Data submission and subsequent sharing for research are consistent with ICF Plan for de-identifying data is consistent with GWAS policy Risks to individuals, families, groups/populations have been considered Genotype and phenotype data were collected in a manner consistent with 45 CFR Part 46.

Clarification/enhancement to various WPPs XVII-1 Research Subjects with Limited English Proficiency (LEP) “…not only clinical criteria determine study eligibility. If the subject's probability and magnitude of risk of participation is great because of language constraints, the prospective subject may not be considered eligible for the study.” XVII-16 Planned Emergency Research, Exception from Informed Consent, and Waiver of Applicability of Informed Consent “…WPP supplements the FDA Draft Guidance and federal regulations at 21 CFR … for…the EFIC protocol…Areas of emphasis are: 1) preliminary approval of the protocol, 2) approval of a community consultation plan, 3) approval of public disclosure, 4) approval of the research to begin enrollment.

Processes, structure, reminder Electronic submission – here in a year! IRB Leadership and Enhancement Committee (ILEC) – Chairs, representative investigators and IRB non-affiliated members, devoted to decision making and consistency; appeals process Reminder: CITI Refresher due by end of 2009 for courses taken in 2007 or before