Orientation to Clinical Research at USC. Randolph Hall Vice President, Research

Transcription

1 Orientation to Clinical Research at USC Randolph Hall Vice President, Research

2 Growing Clinical Research at USC Expand access to novel and promising therapies, and build reputation as center for innovative and effective patient centered care. Expedite execution of clinical trial agreements, and create master agreements with major sponsors. Improve research IT, with clinical trial management system, clinical data warehouse, supplementing TARA Increase knowledge of how to conduct trials

3 Aims of Training Overview of processes for planning and executing research for human subjects in the clinical setting, at USC. Introductory level understanding of all aspects of clinical trials Course is for: New clinical investigator Research coordinators All others who participate in executing a clinical research study

4 Contributors Clinical and Translational Science Institute and its Clinical Trials Unit Cancer Investigators Support Office Office for the Protection of Research Subjects Office of Compliance Clinical Trials Office Office of Research

5 Certificate of Completion Awarded after attendance in entirety at both sessions Demonstration that you have received training on basic processes for clinical research at USC. Not based on examination. If you are unable to attend both sessions, we ll have a record of the one you attended. You may complete the certificate during next course offering in the spring (date to be determined). Certification of completion not currently required, but may be in future.

6 Other Training at USC ( Human subjects protection training Good Clinical Practice HIPAA Training Responsible Conduct of Research Conflict of Interest Grants Management

7 Follow-up Training and Certification Outside USC Association of Clinical Research Professionals: Professional development program, in person and online Certified Research Associate, Certified Research Coordinator, PI Certification, CTI Certificate Society of Clinical Research Associates Professional development programs, in person and online Certified Clinical Research Associate MAGI (Model Agreements and Guidelines International) Clinical Research Contract Professional Certifications Depend on Passing Exams

8 Future Offerings at USC Clinical Trials at USC Orientation: Offered Again in Spring, Date TBD (thereafter, likely once per year) Clinical Trials Administration: Offered First Time Later this Fall, Date TBD

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10 DAY 1 WEDNESDAY, SEPTEMBER 18, 2013 TIME TOPIC INSTRUCTOR 8:00 am 8:10 am Introduction Randolph Hall 8:10 am 8:30 am Clinical Research at USC: An Overview Silvia da Costa 8:30 am 9:45 am Contracting, Financial Management Soheil Jadali and Budgeting 9:45 am 10:15 am BREAK 10:15 am 10:45 am Compliance: Considerations Related Dan Shapiro to Clinical Trials 10:45 am 12:00 pm IRB and Human Subjects Protection Susan Rose

11 DAY 2 WEDNESDAY, SEPTEMBER 25, 2013 TIME TOPIC INSTRUCTOR 8:00 am 9:00 am Planning Research Anthony El Khoueiry 9:00 am 9:30 am Coordination of Ancillary Services Anthony El Khoueiry 9:30 am 10:00 am BREAK 10:00 am 12:00 pm Coordinating a Study Anthony El Khoueiry

12 Orientation to Clinical Research at USC Silvia da Costa, PhD Director, Faculty Research Relations Office of Research

13 Office of Research

14 Office of Research

15 Supplementary Material

16 Supplementary Material

17 Supplementary Material

18 Supplementary Material - Handout CLINICAL TRIAL ORIENTATION: SUPPLEMENTAL MATERIALS Supplemental materials to the Clinical Trials Orientation will be posted at the USC Office of Research website ( to clinical research at usc/). Documents will include: UNIVERSITY ENTITIES & RESOURCES University Offices & Entities Ancillary Committees Other Entities & Resources CONTRACTING, FINANCIAL MANAGEMENT AND BUDGETING Types of Funding Budget Preparation Proposal Routing and Approval Negotiation of Terms See handout for full list

19 Clinical Research Orientation A brief introduction

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21 Non-Cancer Related Studies - Handout

22 Protocol submitted to istar

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25 Review & approval of language related to injury, compensation & informed consent

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29 Office of Research Please don t forget to fill out the attendance card and drop it off as you leave. Thank you!

30 USC Clinical Trials Office (CTO) Answers to CTO s who, what, when, and how questions Soheil Jadali Director, Clinical Trial Office

31 Your Clinical Trials Office (CTO) Started its work on July 01, 2013 Director Sr. Contract Managers Clinical Trial Financial Administrator (MCA Analyst) Budget Specialists Three main operational components: i. Contract Review, Negotiation, and Execution ii. Medical Coverage Analysis iii. Budget Development and Negotiation Transition from Pre-award to Post-award Billing and Accounting Services Coordinating efforts with other units and departments involved in clinical trial management, including hospital billing and compliance office

32 Clinical Trial Initiation In True 2.0 PI/Research Coordinator responds to all questions and provides mandatory documents (i.e. study protocol, proposed Clinical Trial Agreement if provided, and sponsors first proposed budget) for CTO s review (please refer to True 2.0 training slides). CTO will review the submission to confirm that all required documents and information have been provided (different documents depending on the type of submission i.e. CTA, CDA, or nonindustry MCA request). Once this is confirmed, submission is accepted and assigned to appropriate person (depending on the type of Submission). For example, in the case of a CTA, assignments are made to the Contract Manager and the Financial Administrator responsible to conduct the Medicare Coverage Analysis.

33 Contract Review, Negotiation, and Execution The Contract Manager reviews the proposed agreement. Revised version of the agreement (redlined) is sent back to the sponsor for their review and comments. The goals is to move our processes in a way that by the time there is a mutually acceptable version of the agreement terms, the other components of our processes i.e. Medicare Coverage Analysis and budget development and negotiation are either done or close to be completed. Contract terms, MCA, budget, IRB consistency checklist + IRB approval = Study activation

34 Medical Coverage Analysis Financial Administrator conducts the Medicare Coverage Analysis (MCA) to identify and distinguish cost categories (i.e. S, I, and O). Final MCA document facilitates the generation of Research Order Form that in turn allows proper identification of procedures and the source of their funding for billing purposes. Once the MCA is completed, the Financial Administrator assigns the study to CTO Budget Specialists responsible for PI s department/therapeutic unit for budget development and negotiation in accordance with the MCA.

35 Budget Development and Negotiation The Budget Specialist works with the PI and RC to develop USC s response to sponsor s initial proposed budget. USC s first budget is sent to sponsor; budget negotiation begins. Arriving at a mutually acceptable budget and payment terms with sponsor completes the third component of CTO s activities.

36 Transition from Pre-award to Post-award Billing and Accounting Services Study Activated KC budget summary is sent to DCG KC administrator. Final Agreement and budget information is entered in IRIS. Final documents (executed Agreement, final MCA, and budget are sent to True.

37 Questions?

38 Compliance Considerations Related To Clinical Trials Daniel Shapiro Director, Research Compliance

39 Office of Compliance -- Overview Our charge is to: Help USC faculty and staff understand and comply with the rules applicable to their work. Prevent and detect violations of laws or university policy. Promote ethical conduct as articulated in the USC Code of Ethics.

40 Office of Compliance -- Overview To accomplish our charge, the Office of Compliance: Performs periodic risk assessments Assists in the development of policies and procedures Provides training and education Conducts periodic assessments, monitoring, and auditing Investigates allegations of non-compliance and recommends corrective action when appropriate. The Office of Compliance also oversees USC s Help and Hotline, (213) You can call this number to obtain guidance or report suspected violations of law confidentially.

41 The HIPAA Privacy Rule All USC employees, including researchers and research coordinators, have a legal obligation under the Health Insurance and Portability Act ( HIPAA ) to safeguard and keep confidential health information they access in the course of performing research. In practical terms, what does this mean?

42 The HIPAA Privacy Rule: Legal Requirements Generally, a written HIPAA Authorization must be obtained when conducting a research study using a subject s Protected Health Information, or PHI. In limited circumstances, a HIPAA Authorization is not required, but only in instances where an authorization is not practicable to obtain (i.e. retrospective chart review where contacting former patients is impracticable/impossible. Waivers require IRB review/approval! A partial waiver may also be appropriate if access to PHI is only required to prepare a research protocol, and not to conduct the research itself. USC s template HIPAA Authorization and other HIPAA forms may be found on the USC policies page at: Any modifications to these forms require Office of Compliance review and approval.

43 The HIPAA Privacy Rule: How to Comply Obtain HIPAA training Ensure use of most current version of the informed consent and HIPAA Authorization forms as approved by the IRB. Verify that a research authorization has been signed by each research participant. If there is no research authorization, determine whether IRB has issued a waiver if not, an authorization is required. Remember, a signed informed consent without a signed HIPAA Authorization is NOT sufficient.

44 Conflict of Interest in Research USC encourages its faculty, staff, and students to participate in meaningful professional relationships with industrial and other private partners. However, some of these relationships can create, or appear to create, conflicts of interest. Conflicts of interest do not imply any wrongdoing, but they must be disclosed promptly so that they can be reviewed and managed by the university in partnership with researchers and research staff.

45 Conflict of Interest in Research Several USC policies address conflicts of interest: Conflict of Interest in Research policy: covers outside relationships by individual researchers related to research. Institutional Conflict of Interest in Research policy: covers researchrelated conflicts created by USC s financial interests. Relationships with Industry policy: covers physician s outside relationships with the pharmaceutical or medical device industry. Conflict of Interest in Professional and Business Practices policy: Covers general business and personal conflicts maintained by any USC employee (i.e., familial hires, USC business relationships with companies in which the USC employee maintains an ownership or consulting role).

46 Conflict of Interest in Research With regard to individual research-related conflicts, the following types of outside activity must be disclosed: Payments for service (e.g., consulting, payments for service on a board or advisory committee) in excess of $5,000 per year. Private equity interests (e.g., stocks, stock options not publicly traded), regardless of value Public equity interests of $5,000, except when held in an investment vehicle like a mutual fund. Management roles (e.g., director, officer, or similar position of significant decision-making authority)

47 Conflict of Interest in Research How must conflicts be disclosed? First, the conflict must be noted at the proposal submission stage. Second, the conflict must also be noted in i-star. Third, a complete conflict disclosure must be submitted through disclose, ( USC s electronic system designed to allow for researchers to disclose potential conflicts related to their research. Your user name and password for disclose are the same as your USC NetID and password. For assistance on how to use disclose or make a disclosure, contact the Office of Compliance.

48 Conflict of Interest in Research What happens after a disclosure is made? The disclosure automatically is automatically routed to the Office of Compliance. The Office of Compliance performs an initial assessment, and if a conflict is present, presents the disclosure to USC s Conflict of Interest Review Committee (CIRC) at a monthly meeting. The CIRC reviews the disclosure and formulates a recommendation to the VP of Research on how to manage the conflict if appropriate. The VP of Research makes the final decision, which is communicated to the person with the conflict and the IRB. The Office of Compliance monitors compliance over time.

49 Conflict of Interest in Research How do I follow USC s policies on conflicts of interest? If you are a researcher: Complete on-line conflict of interest training. ( Keep up to date records of all your outside relationships. Disclose any potential conflict promptly by noting it at proposal submission and in i-star, and make a complete disclosure in disclose. Cooperate in the Office of Compliance s assessment. Follow any management plan put in place to manage conflicts. Seek guidance from the Office of Compliance if you are not certain whether a particular relationship creates a conflict.

50 Conflict of Interest in Research If you are a research coordinator: Complete on-line conflict of interest training. ( Encourage investigators to promptly disclose outside relationships related to research in disclose. Ask the investigator to complete the portion of the i-star submission addressing conflicts of interest. Help ensure management plans are followed (e.g. when a management plan requires that informed consent be obtained by someone other than the conflicted investigator). If you have any financial interests that may create a conflict on a study, inform the investigator with whom you work.

51 Confidentiality Agreements and Clauses Researchers may need to receive confidential or proprietary information from a sponsor/third party, including: Protocols, investigator s brochure and written instructions Information that is not published Oral disclosures of confidential information Data from the study

52 Confidentiality Agreements and Clauses Many times, this information is provided through via a confidential data agreement (CDA) or nondisclosure agreement (NDA). These agreements may be found within: A clinical trial agreement (CTA) Technology license Data sharing agreement Material transfer agreement (MTA)

53 Confidentiality Agreements and Clauses CDA s/ndas: Will define the information that is to be protected May be one-way, or unilateral for example, the sponsor may want to provide a researcher with information so the researcher can determine whether he/she wants to participate in the research Technology license May also be two-way, or mutual for example, both parties agree to exchange information and keep it confidential At USC, CTO reviews and signs CDA/NDA agreements related to the provision of confidential information.

54 Confidentiality Agreements and Clauses Other confidential information related to clinical trials: Sponsor-provided Protected Health Information (PHI) Certificates of Confidentiality NIH issued document to protect identifiable research information in sensitive areas of research (e.g., sexual attitudes or preferences, information related to the use of illegal drugs, genetic information. Certificates of Confidentiality -- OPRS Guidance.

55 Confidentiality Agreements and Clauses Roles/responsibilities of research coordinators and researchers: Review the Guide to Confidentiality Determine whether confidential/proprietary information is to be provided Become familiar with all restrictions Work together to ensure necessary protections are in place Do not share confidential information outside USC, or inside USC to those not involved in the research Contact the Office of Compliance for guidance.

56 Questions?

57 Clinical Trials at USC Protecting Human Research Subjects Susan L. Rose Executive Director Office for the Protection of Research Subjects

58 So What is a Clinical Trial? A study involving an unapproved FDA regulated test article and one or more human subjects and/or the results are intended to be submitted later to the FDA as part of an application for a research or marketing permit.

59 USC Human Subjects Protection Program The USC Human Subjects Protection Program (HSPP) Consists of the Office for the Protection of Research Subjects (OPRS) and the four USC Institutional Review Boards (IRB).

60 Human Subjects Protection Program Organizational Chart President Chief USC Executive Provost For all academic and research programs Sr. Vice President Administration Legal counsel, institutional compliance Clinical Trials Office Vice President for Research (VPR) Research advancement Office of Compliance (OOC) Regulatory issues Negotiates and manages industry contracts Office for the Protection of Research Subjects (OPRS) Policies, education, reaccreditation, oversight Health Sciences IRB (HSIRB) Reviews biomedical research University Park IRB (HSIRB) Reviews socio behavioral research

61 Office for the Protection of Research Subjects (OPRS) Directs the USC Human Subjects Protection Program (HSPP) (including UPC/ HSC IRB) Designs/distributes widely requested educational materials Ensures compliance with state and federal regulations governing research Develops and maintains policies uniform with research ethics, best practices, and federal regulations Maintains national prominence for USC, leads national flexibility coalition

62 Human Subjects Research Defined Research: A systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge Human Subject: Living individual(s) about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual or (2) identifiable private information. (OHRP) An individual who is or becomes a participant in research, either as a recipient of a test article or as a control. A subject may be a healthy human or a patient (FDA)

63 Human Subjects Research Regulatory Authorities OHRP FDA Federal office overseeing institutions with Federalwide Assurance to comply with the Common Rule (45 CFR 46) Issues guidance on informed consent, conflict of interest, federal reporting requirements, and other topics Regulates clinical research on drugs, devices, and biologics Conducts audits and issues guidance for IRB, investigators, and industry California State Law Contains statutes governing human experimentation, AIDS research, research with prisoners, and embryonic research among others USC Institutional Policies and Procedures Address all aspects of review, conduct, and oversight of human subjects research at USC

64 OHRP Office for Human Research Protections (OHRP) oversees system to protect the rights, welfare, and wellbeing of subjects involved in research, ensures research is carried out in accordance with regulations 45 CFR part 46. Provides direction in human subjects research through guidelines, interpretation of regulations, and monitoring compliance. Regulations/Policies Federal Regulations for the Protection of Human Subjects Informed Consent Requirements Informed Consent Requirements in Emergency Research

65 FDA Responsible for assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation s food supply, cosmetics, and products that emit radiation. Research studies involving human subjects must comply with federal regulations (21 CFR 50). FDA regulations pertaining to human subjects research include: Protection of Human Subjects (21CFR 50) Financial Disclosure by Clinical Investigators (21CFR 54) Institutional Review Boards (21CFR 56) Investigational New Drug (21CFR 312) Biological Products (21CFR 600) Investigational Device Exemptions (21CFR 812)

66 Health Insurance Portability and Accountability Act (HIPAA)/Privacy Rule HIPAA, known as the Privacy Rule, was designed to protect the privacy of health information. HIPAA protections are in addition to existing state laws. California laws provide extra protection to patients and include civil and criminal penalties for non-compliance. Protected Health Information (PHI) Identifies or could identify an individual with respect to health records Is created or received by a healthcare provider, health plan, or healthcare clearinghouse

67 USC Submission Process for Clinical Investigation/Trials Research Coordinator/P.I. obtains istar account Takes required training Complete and submit application incl. Informed Consent Obtains departmental review IRB/Ancillary Committees Review PI/RC address contingencies Submit amendments, continuing review, adverse events Study Closeout

68 Human Subjects Protection Program: USC Required Training Human Subjects Protection PI and key personnel conducting Human Subjects research Good Clinical Practice (GCP) Health Insurance Portability and Accountability Act (HIPAA) Responsible Conduct of Research (RCR) PI and key personnel conducting clinical research PI and key personnel who have access to private identifiable health information (e.g. health records) Recipients of certain NSF, NIH, PHS awards. Recommended for all involved in research Conflict of Interest (COI) Investigators receiving HHS funding Visit for more info

69 Summary of istar Application istar is the IRB application system used to Create and submit IRB applications Correspond with the IRB, respond to requests, and receive approval notices Submit annual/ or semi-annual applications for review as required Report protocol deviations, subject complaints and other unanticipated events.

70 View of istar Workspace

71 Departmental Review Required for all research submitted to the Health Sciences IRB In istar, Dept chair attests to: Scientific merit and feasibility of the study Availability of needed resources to conduct the study Departmental acceptance of the study

72 Ancillary Committees Oversight bodies (separate from IRB) involved in review and approval of research. Conflict of Interest Review Committee (CIRC): Evaluates and manages conflicts in research Data Safety Monitoring Board (DSMB): Reviews Data Safety Monitoring Plans, safety, and scientific progress Radiation Safety Committee: Evaluates safety of research with radioactive materials and radiation-producing equipment Pathology Department (LAC+USC): Receives requests for specimens, confirms that appropriate consent and authorization has been obtained for each specimen Cancer Center Clinical Investigations Committee (CIC): peer review body to evaluate feasibility, scientific merit and adequate resources for studies at Norris Cancer Center.

73 IRB Review and Approval An IRB (Institutional Review Board) reviews research involving human subjects Three IRB at HSC (biomed) One IRB at UPC (soc-behavoiral) An IRB reviews: Risks and benefits to subjects Vulnerable status of subjects Privacy and confidentiality Conflict of interest Informed consent content and process Scientific merit HIPAA requirements (IRB fulfills role of privacy board)

74 Levels of IRB Review Full Board Expedited More than minimal risk to subjects Not covered under other review categories Example: interventions involving physical or emotional discomfort or sensitive data Not greater than minimal risk Fits one of the 9 Expedited Review Categories* Examples Collection of biospecimens by noninvasive means Exempt Less than minimal risk Fits one of the 6 Exempt Categories* Example: Chart review studies *Defined by federal regulation (45 CFR 46)

75 Minimal Risk Minimal risk means that the probability and magnitude of harm or discomfort is not greater than what is encountered in daily life or routine physical or psychological examinations. Risk reflects the ratio of risks to benefits that a subject will encounter by choosing to participate in a research activity

76 Balancing Risk/ Benefit Ratio Benefit: A valued or desired outcome; an advantage. Risk: The probability of harm or injury (physical, psychological, social, or economic) occurring as a result of participation in a research study. Subjects should be made aware when research offers no direct benefit. Risk should always be minimized. Notify the IRB whenever risks change in a study

77 Informed Consent Requirements The informed consent process must: Explain benefits/risks/procedures posed to subjects Distinguish between research and standard medical care Answer questions from subjects Minimize possibility of coercion/undue influence Provide subjects with adequate time to consider participation Be presented in language understandable to the subject Allow subjects to refuse or discontinue participation at any time Respect subject s physical, emotional and psychological capacity, and vulnerable status

78 Informed Consent Informed consent (IC) is process used to enroll a subject to a study. Method and documentation of consent varies according to level of review and nature of the research. Informed Consent Template - Parental Permission authorization from a parent or guardian for a minor Child/Youth Assent authorization from subjects who are minors, parental permission must also be obtained Short form authorization form for subjects who do not read English Waiver of documentation /element permitted when documentation (IC) linking the subject to the study would pose a risk to the subject Information/Fact Sheet provides study information to subjects when a consent form is not required

79 Vulnerable Populations Vulnerability is situational and individual Pregnant Women/Fetuses* Comatose patients Prisoners* Cognitively impaired Children* Employees/Students Homeless *Federal categories of vulnerability Vulnerability implies a power differential Vulnerable subjects MUST receive extra protections

80 Privacy and Confidentiality PRIVACY Subject allows extent, timing, and circumstances of sharing personal information/data with others. Subject expects information given in a relationship of trust not to be divulged to others without permission. CONFIDENTIALITY Refers to data/specimens and how identifiers/privacy are maintained. Methods include data inscription, password protection, locked storage, and coding samples and data.

81 Responsibilities After IRB Approval Amendments: changes to IRB approved research must be approved by the IRB before being implemented Reportable Events: subject complaints, unanticipated problems, adverse events, or protocol violations must be reported Continuing Review: periodic review of an IRB approved protocol (at least annually) Study Closeout: Process by which a study is ended and final status report is submitted

82 Terms to Know Significant New Information/Findings (SNIF): Information developed during the course of research that may affect subjects willingness to continue participating Data Safety Monitoring Plans/Board: independent evaluation of study data to assure safety and reporting of adverse events Certificates of Confidentiality: documents issued by the National Institutes of Health (NIH) to protect sensitive identifiable research information from compelled disclosure (eg: illicit activities)

83 Clinicaltrials.gov: FDA mandated online registry of applicable clinical trials

84 Who Can I Contact for Help? Office for the Protection of Research Subjects (213) oprs@usc.edu oprs.usc.edu Office of Compliance (213) complian@usc.edu ooc.usc.edu Health Sciences IRB (323) irb@usc.edu oprs.usc.edu/hsirb/ Clinical Trials Office (323) sjadali@usc.edu research.usc.edu/clinical-trialsat-usc/