Almost Ready: Before a Study Starts

1. Almost Ready: Before a Study Starts HIC/YCCI/GCA June 26, 2008

2. Introduction • Joint session as a response to a survey conducted this spring by HIC and YCCI • We’ve divided our presentation into two sections: You Have an Idea Your Idea was funded/supported

3. You have an idea: What do you do first? • Process is not totally linear! • Be a toddler and learn how to parallel play!

4. You Have An Idea: How will you fund it? • Do you have a funding source? http://info.med.yale.edu/ysm/grants/funding_opportunities/ • Types of Funding Sources • Federally Funded • Foundation Funded • Industry Funded • Departmentally Funded and other • State

5. You have an Idea: How will you design it? • Design: The general framework by which the study will be undertaken. • Two main categories: • Observational • Experimental • Study subjects: balance of feasibility and generalizability • Do you have these patients within your clinical population? • Statistical Issues: There is uncertainty when a sample is used to describe what is happening in a population • Sample size & Power Calculations • Plan for Analysis of Each Aim

6. You have an Idea: Do you have enough money & resources? • If your design is feasible/sound and you have access to the patient population, can the proposed funding source and site afford your idea? • Do you have a budget? Is the study feasible for your site? • Per Patient Costs (SOC vs. Research) • Additional Costs (e.g. Pharmacy, IRB review, recruitment, subject payments) • Do you need labs? What kind, prep and rationale, shipping? • Does your protocol require specialized nutritional needs/interventions? • Data management needs; storage needs for data and supplies • “Hidden” costs • Internal and external budget development • Personnel needs (Who, What, When, Why?) • Appropriate Venue, i.e. site visits (Where?) • Indirect (F&A) costs

7. You have an idea: So you like to write?Pre-HIC considerations • Aims or Study Objective and Research Plan need to match and be feasible in humans • What are the regulatory requirements for your project? To which IRB will you submit? • Does your research include a test article? Do you need an IND or IDE from the FDA? • Do you need to complete/gather other regulatory documents, e.g. FDA 1572 form, CVs, lab norms, financial disclosure(s)? • Do you need to write Standard Operating Procedures for your site or a Manual of Operating Procedures for your study? • All human subjects research needs a Data and Safety Monitoring Plan. How will you secure your data?

8. You have an idea: It’s all in the data! • How will you collect your data? Electronic or paper • Case report forms—the “deliverable” of the study. Do you need to develop your own or is the sponsor providing them? • Source documents—any document where data is first recorded. Identify the source documents that will be needed for your study. Are there gaps in what is institutionally available? • What are your database needs? • Desktop tools—Excel or Access • Low-end Web Based Solutions—web-based forms designed by research team with the help of informatics • High-end Web Based Solutions—e.g. Trial DB, a secure system that can generate sophisticated forms; secure entry of PHI data on web; needs a bioinformatics designer.

9. You have an idea: Where can you get help? • Yale Center for Clinical Investigations has service units to assist with your idea: http://www.ycci.yale.edu • Applicable Service Units include: • Biostatistical Support Unit (James Dziura, PhD & staff) • Budget Development Unit (Lynn Mezzanotte & Lane Campbell) • Protocol Development & Regulatory Support Unit (Melody Sacatos) • Bioinformatics (Pradeep Mutalik) • CONTACT: Theresa Katz, Protocol Process & Committee Coordinator 785-6335 or theresa.katz@yale.edu

10. GCA: What Do We Need? • PI/Dept. to notify their GCA reviewer of possible study • PI/Dept. to provide paperwork or email contract.med@yale.edu • A company protocol if Industry sponsored • A company contact if industry sponsored • A scope of work if PI initiated • The Proposal Summary and Transmittal Form • A Department Contact • The HIC protocol • A budget (may not be immediately available)

11. Federally sponsored clinical trials • Often driven by RFP • May require subcontracting • Talk to your GCA reviewer

12. GCA: What Do We Do? • Start a file and enter study into our database • Verify contract/grant terms • Verify regulatory compliance • Compare and integrate informed consent and contract language • Negotiate with sponsor and come to resolution • Wait for final budget, if still under review, making sure delineation has been made between standard of care and research services • Sign contract/grant

13. GCA: What Drives the Process • Protecting the University from risk • Ensuring that any Yale inventions are protected • Making sure the University/PI is not making promises it can’t keep • Defining confidential information in a logical fashion • Safeguarding rights to publication

14. GCA: What Do Sponsors Want? • Just about everything and on their terms • Publication review • Broad licensing terms • Coverage for subject injury • Payment based on enrollment • Indemnification protection • …but primarily, they want fast turnaround

15. GCA: What Do We Aim For? • Establishing relationships with each Sponsor as it is likely we will deal with them again soon • A Win-Win for Yale and the Sponsor • A fair and equitable budget to cover trial costs and sometimes hidden costs • Coverage of costs for treatment of adverse events

16. You Have An Idea—HIC 1 • You may not be sure if your idea needs HIC review • Some studies are exempt—but the exemption must be applied for • A medical records review needs to come to HIC • Your idea has some aspects that you think pose human subject protection questions • Your study may be controversial, or it may have issues in getting consent, or you may be establishing a repository and need to determine its parameters.

17. You Have an Idea—HIC 2 • You’re not sure where to start for HIC approval • Is there a process? How do you find out what the process is? • Your idea includes people not associated with Yale • Yale’s approval generally covers only Yale agents or employees; arrangements must be made

18. You Have an Idea--HIC 3 • Are you a resident, fellow or trainee? • You’ll need a faculty sponsor—the application has a place for the faculty sponsor to agree and sign. • Do you meet faculty guidelines for being PI? • Guidelines are available on our web site. If you don’t meet them, special permission must be sought. • GCA has an exemption form posted on their website. CALL US FOR A CONSULT

19. Your Idea Was Funded—HIC 1 • Find a primary reviewer • review the list on the website. You may choose someone in your area, or someone whose background is similar to the research area your protocol involves; all members know the human subjects protections • Call them and ASK if they would be a primary reviewer. Committee members are volunteers; the first person you ask may already be committed to primary review other protocols. • Discuss with them how they will work with you—what communication system is needed.

20. Your Idea Was Funded—HIC 2 • Have everyone on your protocol complete the required training • If someone is listed on your protocol, they must complete human subjects protections training and HIPAA trainingfor researchers

21. Your Idea Was Funded—HIC 3 • Check the HIC web site for the most current forms • evolving practice and regulation mean that forms often require updating. Pull the form from the website for each submission. • Develop all the materials you’ll need: ads, phone scripts, information sheets, informed consent documents, wallet cards • If you develop materials after approval, they must be submitted as an amendment.

22. Your Idea Was Funded—HIC 4 • Identify all review requirements before/in addition to HIC • PRC? MRRC? PPRC? RSC? YCCI? WHVA? • In a complex system, more than HIC review is often required. Check the HIC Protocol Application instructions. • Plan the timeframe • It’s longer than you’d like. The more you know the process and the more organized you are, the faster it goes.

23. Your Idea Was Funded—HIC 5 • When Completing your protocol application • Use the most current form • As noted earlier, forms change. Check the web. • Get all the necessary signatures • Everyone on the protocol. The faculty sponsor if there is one. The department chair. Or chairs, if the study involves more than one department. The primary reviewer. • Include the relevant portions of the grant • The cover page, aims and human subjects sections only.

24. Your Idea Was Funded—HIC 6 • Complete the protocol-related COI questions • Don’t check the boxes in advance for the researchers, and just have them sign. Each person on the protocol must sign and check their own box. • Indicate ALL funding sources • Studies often have multiple funders. The HIC needs to know all funders for each protocol. Our information must match G& C information. This also helps the researcher identify whether or not they have a protocol-related COI.

25. Your Idea Was Funded—HIC 7 • Make sure the informed consent information matches the protocol • Do the procedures match? Does the In Case of Injury language match the contract? • Do you need a Certificate of Confidentiality? • Make the correct number of copies • Check the How Many Copies Instruction on the website. • Include all required materials. • The HIC can no longer hold documents while awaiting further materials.

26. Your Idea Was Funded—HIC 8 • Don’t forget HIPAA requirements • Do you need a waiver? • Do you need a RAF? • Do you need a combined consent/RAF?

27. Your Idea Was Funded—HIC 9 Check our website: http://info.med.yale.edu/hic/ Bookmark our forms page: http://info.med.yale.edu/hic/forms/index.html Call when you have questions 785-4688

28. Your Idea Will Be Supported: GCA • You have HIC approval • A fully negotiated contract is in place • Study enrollment can begin • Contact GCA by email to request setup of an At Risk Account • GCA will forward the request to the ASU who will check compliances and setup the account • Upon receipt of the first check, the account will be taken off of the At Risk list

29. Your Idea was funded: The Protocol • Does your protocol contain all procedures and/or interventions? Do you need an amendment before implementation? • Did you answer “yes” to the question on the HIC application, “Will your research study require clinical care services to human subjects that may be billable to the subject, the sponsor, or other third party payer?” If so, did you complete the form(s) on the YMG website at http://yalemedicalgroup.org/comply/alert/Research.htm • Once HIC approved, have you registered your trial on clinicaltrials.gov? [Needed for applicable trials and for publication in journals belonging to the International Committee of Medical Journal Editors (ICMJE)]

30. Your idea was funded: Implementation • Study meetings with your team early & often. • Who will do what and when? If the YCCI/HRU, contact your Protocol Coordinator to help facilitate. • Delegation of Authority—Communicate with PI & ensure accountability for each study component in accordance with GCP or as applicable to your study. • Does everyone on the team have the proper training and understand the protocol? (Remember to document all training!) • Do you have all CRFs, study and regulatory binder(s), test articles (e.g. IDS), storage for files/kits, shipping materials, and SOPs/MOPPs as applicable? • Have you re-contacted all parties involved to give them enough time to plan for your study? Timely communication is KEY! • Parallel play again! Team members may meet with different departments/service units and then report back to study team/PI.

31. Your idea was funded: Specifics of Implementation • YNHH CLIA approved labs, if needed: Have you filled out the Dept of Lab Medicine Request for Services or Specimens Form with your T account (hospital charging)? • Research Labs: Have you contacted the University Lab and discussed requirements, labeling, processing, and analysis? • If YCCI Core Lab, contact Ralph Jacob at 54422. • Recruitment: Have you covered your bases or do you need more modalities? • Does the team need to conduct a mock visit/session? (Often helpful for complicated studies esp. those involving multiple interventions and/or scanning.)

32. Your idea was funded: Where can you get help? • Yale Center for Clinical Investigation has service units to assist you with study implementation. • Applicable service units include: • Education &Training of Research Staff (Gina D’Agostino) • Recruitment & Marketing (Kelly Burton & Tracy Yale) • Hospital Research Unit (Shelley Britt & Bill Hofmann) • Church St. Research Unit (Diane Wall) • YCCI Core Lab (Ralph Jacob) • Bionutrition Core (Donna Caseria & Mary Savoye) • CONTACT: Theresa Katz, Protocol Process Coordinator at 785-6335. References: Woodin, K.E. (2004).The CRC’s Guide to Coordinating Clinical Research. Boston, MA: Thomson Centerwatch. Dziura, J. (2007). YCCI Pilot Project Award Orientation. September 20, 2007.

33. Your idea was funded: Best of Luck! • If necessary, have a debriefing after your first study visit. • If debriefing not necessary, have a celebration! • Best of luck with all your current & future studies!