Clinical Research at MSU

Transcription

1 Financial Administration Development Program: Clinical Research at MSU Kristen Burt, Office of Regulatory Affairs (ORA) Sharon Schooley, Clinical & Translational Sciences Institute (CTSI) February 24, 2017

2 Why is Clinical Research Important? Key component of translational research Improve health and expand knowledge New discoveries lead to new treatments Important funding mechanism MSU research goals Collaboration between MSU and hospitals 2

3 MSU External Funding- Sources Source: 3

4 MSU External Funding- Trends Source: 4

5 MSU External Funding- Trends Source: 5

6 Research Project Grant investigators Applicants, awardees, and funding rates NIH Data Book ( Data provided by the Division of Statistical Analysis and Reporting Branch

7 NIH Awards Fiscal Year 2016: Research Project Grants to Domestic Institutions of Higher Education Source: 7

8 NIH Awards Fiscal Year 2016: Research Project Grants to Domestic Institutions of Higher Education Source: 8

9 Why is Clinical Research Important to You? 1. Financials- Are different from typical grants because payments may be tied to participants- if you don t enroll participants, you don t get paid 2. Regulatory- Different responsibilities apply depending on the type of project and whose idea it is 3. Metrics- Correct project nature ( activity type in Kuali Coeus) is crucial in reporting on institutional research activity and funding 4. Status/Ranking- Incorrect reporting affects our ranking against other institutions 9

10 Does any part of your job involve clinical research and/or clinical trials? A. Yes B. No 10

11 Objectives Understand translational research and apply definitions related to clinical research and clinical trials Recognize how processes differ for clinical research and clinical trials Identify who to contact at MSU with questions 11

12 What Does it All Mean?? 12

13 Do you know what translational or clinical research is? A. I don t have a clue B. I might have a vague idea C. I have some knowledge D. I have a fair amount of knowledge E. I would consider myself well-educated in this area 13

14 Have you participated in a research study before? A. Yes B. No 14

15 Idea Animals Humans Disseminate Post Dissemination Review Overview of the Translational Research Process See Handout for Detailed Diagram 15

16 A Translational Research Story: Idea, Animals ( Bench Research): In 1965, Barnett Rosenberg and coworkers at MSU discovered platinumcontaining compounds that inhibited cell division and cured solid tumors resulting from cancer Humans ( Bedside ): The discovery led to Cisplatin, a chemotherapy drug that underwent clinical trial testing for safety and effectiveness Disseminate ( Practice, Policy ): Cisplatin was approved by the FDA in 1978, and was the first platinum compound chemotherapy developed. It is commonly used today in the treatment of many types of cancer MSU developed Carboplatin in 1989, a similar drug which has less side effects. 16

17 Why Are Definitions Important? Federal regulatory requirements Grants policy requirements Proposal submission- project nature/activity type Facilities & Administrative Costs Contract negotiations Regulatory reviews Institutional metrics 17

18 Idea Animals Humans Disseminate Post Dissemination Review 18

19 Basic Research A systematic study directed toward greater knowledge or understanding of the fundamental aspects of phenomena and of observable facts without specific applications towards processes or products in mind... 1 Driven by a scientist's curiosity or interest in a scientific question. The main motivation is to expand man's knowledge, not to create or invent something CFR 272.3; 2 Partially taken from Lawrence Berkeley National Laboratory, 19

20 Idea Animals Humans Disseminate Post Dissemination Review 20

21 Research Involving Animals Animal Care Program at MSU Campus Animal Resources Institutional Animal Care and Use Committee Provides regulatory and administrative oversight for animals used in teaching and research endeavors Annually, the MSU community cares for over 50,000 animals from a wide variety of species 21

22 Idea Animals Humans Disseminate Post Dissemination Review 22

23 Research Involving Humans Human Research Protection Program at MSU Institutional Review Board Offices Compliance Office Institutional Review Boards The IRB reviews and approves research studies that involve people before the research can start In 2016, there were approximately 1,200 new projects approved, with approximately 20% biomedical 23

24 Have you completed an application for approval to conduct human research to a MSU Institutional Review A. Yes B. No Board (IRB)? 24

25 Human Research Clinical Research Clinical Trial Clinical Investigation 25

26 Human Research Clinical Research Clinical Trial Clinical Investigation 26

27 Human Subject Living individual about whom an investigator conducting research obtains: data through intervention or interaction or identifiable private information 1 Research Systematic investigation designed to develop or contribute to generalizable knowledge 2 Contact the MSU HRPP 1 45 CFR (f); 2 45 CFR (d) 27

28 Human Research Clinical Research Clinical Trial Clinical Investigation 28

29 Clinical Research Patient-oriented research: This type of research involves a particular person or group of people or uses materials from humans. Epidemiological and behavioral studies: These types of studies examine the distribution of disease, the factors that affect health, and how people make health-related decisions. Outcomes and health services research: These studies seek to identify the most effective and most efficient interventions, treatments, and services. 1 1https://grants.nih.gov/grants/glossary.htm 29

30 Human Research Clinical Research Clinical Trial Clinical Investigation 30

31 Clinical Trial Prospectively assign individuals to one or more interventions to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. 1 See Handouts for Expanded Definition and Decision Tree Contact the MSU HRPP with questions related to clinicaltrials.gov and training 1https://grants.nih.gov/grants/glossary.htm 31

32 Clinical Trial Phase 1 and 2 Phase # Subjects Length Purpose % Drugs Successfully Tested Several months 2 Up to several hundred Several months to 2 years Mainly SAFETY 70 Some shortterm safety, but mainly EFFECTIVENESS 33 32

33 Clinical Trial Phase 3 and 4 Phase # Subjects 3 Several hundred to several thousand Length Purpose 1-4 years Safety, effectiveness, DOSAGE % Drugs Successfully Tested Varies Varies Monitor effectiveness, collect ADVERSE EVENTS 33 NA

34 Human Research Clinical Research Clinical Trial Clinical Investigation 34

35 Clinical Investigation Any experiment that involves a test article (e.g. drug, device) and one or more human subjects that meets certain requirements per the U.S. Food and Drug Administration (FDA) 1 Requires MSU IRB review and approval and may involve other FDA requirements. Contact the MSU HRPP 121 CFR

36 Idea Animals Humans Disseminate Post Dissemination Review 36

37 Disseminate Results distributed (e.g. peer reviewed journals, clinicaltrials.gov, media) Translation to policy and practice New treatments Changes to existing processes New drugs and devices become available for physicians to prescribe New health policies and practices are implemented 37

38 Another Example: Michigan Keystone ICU project- 67 hospitals Changing behavior through use of a short safety checklist when inserting catheters into patients Resulted in a significant reduction in bloodstream infections in Michigan Estimated to have saved 1500 lives, $200 million in the first 18 months of the study Leading to new policies and practices for infection control 38

39 Idea Animals Humans Disseminate Post Dissemination Review 39

40 Post Dissemination Review Outcomes research Phase 4 clinical trials After approved for marketing Evaluate the long-term effects for a greater number of patients Monitor effectiveness Monitor adverse events 40

41 So: We know what type of project it is But Who s idea/protocol is it ( initiator )? MSU researcher? NIH, NSF, NCI, Industry, etc.? Researcher from another institution? 41

42 MSU Initiated Initiates and conducts an investigation. Agency Initiated Initiates and takes responsibility for the research. Assumes all of the sponsor responsibilities as applicable. MSU has no direct input on or influence over research design. Includes another institution who asks MSU to participate in their investigatorinitiated research. 42

43 Will you be submitting proposals through Kuali Coeus (KC), formerly the e- Transmittal process? A. Yes B. No 43

44 Putting it all together: Project Natures (Activity Types in KC) Clinical Research with Human Subjects that is: Agency Initiated or MSU Investigator Initiated Clinical Trial with Human Subjects that is: Agency Initiated or MSU Investigator Initiated Non-Clinical Research with Human Subjects Kuali Coeus incorporates processes to help correctly choose the activity type and initiator Contact CTSI, HRPP (regulatory definitions), or the Office of Sponsored Programs 44

45 Why Focus on Project Natures/Activity Types? Project natures/activity types drive research metrics Investigator-initiated research activity Funds attributed to clinical research Funds attributed to clinical trials Research activity in general External agency activity Human clinical trials may have additional regulatory requirements 45

46 An MSU researcher would like to take tissue samples from deceased individuals for research. Does this activity involve human subjects? A. Yes B. No 46

47 Case Studies 47

48 Case Study #1 An industry sponsor has contracted with an MSU investigator to collect data from patients already using the sponsor s blood coagulation product as standard of care. Participating in the study will not dictate the course of therapy, other than to be eligible for the study the patient has to already be using the sponsor s product. The purpose of this observational study registry is to get information on routine clinical care for patients with the blood clotting disorder. Is this study a clinical trial? What project nature / activity type is this study? 48

49 Case Study #2 A study is designed by an MSU researcher to randomly assign individuals to either an experimental intervention to promote weight loss, or to a control intervention. After a year, participants behaviors will be assessed to measure their adherence to exercise regimens. Is this study a clinical trial? What project nature / activity type is this study? 49

50 Questions? 50

51 Overview of Clinical Research/Trial Process 51

52 What and Who are Involved? Other Regulatory Staff (HRPP) Administration (Agreements, Budget & Billing) Principal Investigators The Process Study Staff Sub- Investigators Internal & External Resources 52

53 Decision to Pursue Confidential Disclosure Agreement Protocol Feasibility Study Completion Closeout Record Retention Study Pre-Award Parallel Processes Budget Preparation Agreements and Negotiation Regulatory Reviews Study Start-Up and Management Financial Contractual Regulatory 53

54 Decision to Pursue Confidential Disclosure Agreement Protocol Feasibility Study Completion Closeout Record Retention Study Pre-Award Parallel Processes Budget Preparation Agreements and Negotiation Regulatory Reviews Study Start-Up and Management Financial Contractual Regulatory 54

55 Confidential Disclosure Agreement (CDA) Legal contract that governs the exchange of proprietary or confidential information, used to: share proprietary information with an external party for a limited purpose while protecting it from being disclosed to others or the public. avoid forfeiture of patent rights due to premature public disclosure. Can only be signed by MSU Technologies CDA: Contact MSU Technologies with questions. Feasibility: Contact CTSI with questions. 55

56 Feasibility An assessment of a project s needs including: Study subject base/recruitment plans Project logistics and available resources Financial obligations Clinical Research is a BUSINESS, requires a strategic plan Business tools can be used for this process Operational budgets, templates, break-even analysis CTSI is available to help 56

57 Decision to Pursue Confidential Disclosure Agreement Protocol Feasibility Study Completion Closeout Record Retention Study Pre-Award Parallel Processes Budget Preparation Agreements and Negotiation Regulatory Reviews Study Start-Up and Management Financial Contractual Regulatory 57

58 Parallel Processes and Regulatory Reviews Department / College Work-Up, Submission: Coverage Analysis (if required) Contract Review by Appropriate Office Submit IRB Application Additional Required Reviews? Obtain All Needed Institutional Reviews &/or Approvals, CGA Account Setup, & Notify All Parties Coverage Analysis: Contact HRPP Compliance Contract Review: Contact Business Connect or Office of Sponsored Programs IRB: Contact HRPP Additional Reviews: Contact appropriate offices 58

59 Budget Preparation Analyze protocol and study documents to determine costs and required study services Create overall study budget including all study costs, e.g. upfront/start up, per-subject, variable, and federal vs industry budgeting parameters Negotiate when possible, e.g. industrial sponsor budgets are generalized across sites Budget Preparation, negotiation: Contact CTSI 59

60 Agreements and Negotiations Liability, publication, intellectual property, subject injury, etc. Includes subcontracts with external service providers Work with the appropriate MSU office (Business Connect, Office of Sponsored Programs) Agreements and negotiations: Contact Business Connect or Office of Sponsored Programs 60

61 Research Award Transactions by Fiscal Year Research Awards Clinical Research/Trial Awards 61

62 Research Award Transactions by Fiscal Year: Clinical Research/Trial Clinical Trial Clinical Research 62

63 NIH Proposals by Fiscal Year Total Proposals Clinical Research/Trial Proposals 63

64 NIH Award Transactions by Fiscal Year Total Awards Clinical Research/Trials Awards 64

65 NIH Award Transactions by Fiscal Year: Clinical Research/Trial Awards Clinical Trial Clinical Research 65

66 Decision to Pursue Confidential Disclosure Agreement Protocol Feasibility Study Completion Closeout Record Retention Study Pre-Award Parallel Processes Budget Preparation Agreements and Negotiation Regulatory Reviews Study Start-Up and Management Financial Contractual Regulatory 66

67 Financial Invoice sponsor per contract/grant Track sponsor payments; review for accuracy Allocate payments based on initial cost projections Pay service providers per billing grid, subcontract, service quotes Study subject stipends and 1099 Effort tracking, labor distributions, & effort reports 67

68 Contractual Be familiar with the executed contract Contract amendments, budget revisions Reporting per contract/grant requirements Track study subject entry, visits, and study event completion Management of study drugs, devices, equipment 68

69 Regulatory Compliance Affects Our Reputation Assure all necessary approvals are in place Follow the IRB approved protocol Follow regulatory submission requirements For FDA projects: Be familiar with regulations and long term impacts The FDA relies on data that sponsors submit to decide whether a drug should be approved 69

70 Decision to Pursue Confidential Disclosure Agreement Protocol Feasibility Study Completion Closeout Record Retention Study Pre-Award Parallel Processes Budget Preparation Agreements and Negotiation Regulatory Reviews Study Start-Up and Management Financial Contractual Regulatory 70

71 Study Closeout and Record Retention Any remaining contractual obligations Regulatory submission requirements Record retention requirements (e.g. contract, regulation), it can be many years (e.g. 25) Reporting per contract/grant requirements Final invoicing, payment allocations Study closeout of finances 71

72 Account Closeouts: Count ,005 1,361 1,381 1, Count Pending Closeouts as of 2/17/2017: 415

73 Account Closeouts: Average Number of Days to Closeout Average Number of Days to Closeout Pending Closeouts as of 2/17/2017: 415

74 REVIEW: Best Practices Contact appropriate office with questions they are here to help! Project feasibility - is the study realistic to do? Correctly assign project natures/activity types - METRICS! F & A rates! Budgeting - assess ALL project-related costs, negotiate if applicable 74

75 REVIEW: Best Practices Complete parallel submission processescontract/grant, IRB, budget processes (i.e. coverage analysis) Have appropriate University offices sign contracts and agreements Proactive post-award management Maintain regulatory compliance 75

76 Does any part of your job involve clinical research and/or clinical trials? A. Yes B. No 76

77 Questions? 77

78 Vice President for Research & Graduate Studies Clinical & Translational Sciences Institute (CTSI) Biomedical Research Informatics Core (BRIC) Develop New Opportunities With Research Partners Office of Clinical Research (OCR) Research Collaboration Data oversight throughout study lifecycle Biologic Sample Collection & Processing Research Process Navigation Project Feasibility / Needs Assessment 78 Data Mgt. & Informatics, Access to Software Tools Data Security & Data Storage Subject Recruitment & Retention Strategies Access to Clinical Research Personnel & Facilities Pre & Post Award Financial Training & Support

79 For additional questions, please contact us Kristen Burt- ORA Sharon Schooley- CTSI 79