INTRODUCTION TO CLINICAL INVESTIGATION Interface with Biomedical Industry

1. INTRODUCTION TO CLINICAL INVESTIGATIONInterface with Biomedical Industry Mary Lee Vance, M.D. Professor of Medicine and Neurosurgery Department of Medicine Endocrinology and Metabolism

2. CLINICAL RESEARCHTypes of Studies • Investigator initiated: proposal submitted to industry sponsor - request drug, financial support or both • Sponsor initiated: usually a multicenter clinical trial; sponsor provides protocol, budget (must be negotiated)

3. CLINICAL RESEARCHRequirements • All clinical studies: must be approved by Human Investigation Committee (IRB) – protocol & consent form • General Clinical Research Center: must be approved by GCRC Advisory Committee (reviewed before IRB review)

4. CLINICAL RESEARCHRequirements Sponsor initiated study • IRB fee to review ($1,250) • GCRC use: inpatient & outpatient: sponsor assumes all costs

5. CLINICAL RESEARCHRequirements Investigator initiated study • No IRB fee to review protocol • GCRC use: no charge for use of inpatient or outpatient facility (some lab charges may be covered, depending on cost – need to consult with GCRC administrator)

6. CLINICAL RESEARCHRequirements • Cannot charge patients for any cost of industry sponsored studies • ? Current policy on conducting studies in outpatient clinic setting …

7. CLINICAL RESEARCHIndustry Support How to participate in a clinical trial? • Need a contact: ask your colleagues; contact research director of a company that is involved with your field…. • Ask your “rep” if he/she knows of any planned studies (usually not helpful, but worth a try)

8. CLINICAL RESEARCHMulticenter Clinical Trial Items to consider BEFORE participation • Is the study scientifically valid? • Does it have potential for publication? • Is the budget adequate? (you don’t work for the pharmaceutical company) • Do you have the resources/time to participate? • Do you have patients you can enroll?

9. CLINICAL RESEARCHMulticenter Clinical Trial You decide to participate – Contract • Have the contract reviewed by Dean’s office before writing the protocol & consent form • U Va has specific requirements & will resolve contract issues directly with the sponsor (Betty Pincus is terrific)

10. CLINICAL RESEARCHMulticenter Clinical Trial You decide to participate – budget negotiations • The sponsor’s budget is usually inadequate • University overhead: 25%; ? Department overhead (10% for Dept. Medicine) • Protocol preparation & IRB review fees • Travel, lodging, parking costs for patients • Professional supervision (your salary support)

11. CLINICAL RESEARCHMulticenter Clinical Trial You decide to participate – budget negotiations • Patient payment: necessary if patient does not benefit from study (e.g. dose finding study or pharmacokinetic study) • Normal volunteer study: must pay for participation • Include: secretarial, mail, fax, telephone, publication costs

12. CLINICAL RESEARCHMulticenter Clinical Trial You decide to participate – budget negotiations • Laboratory: check on discount rate • Radiology: check on discount rate • ECG: check on discount rate • Will need to set up special billing for these charges; billed directly to your grant account

13. CLINICAL RESEARCHMulticenter Clinical Trial Publication • Authorship, order of authorship, control over final manuscript • Should be stated in the contract

14. CLINICAL RESEARCHMulticenter Clinical Trial Investigator Meeting • Required by FDA • 1-2 day session: review of protocol, requirements, discussion • Study coordinator also attends (CRF training)

15. CLINICAL RESEARCHMulticenter Clinical Trial Case Report Forms (CRF) • Sponsor sends monitor before, during & at completion of study to review records, queries • This takes more time than you think: consider adding line item in budget to cover your time; coordinator’s time

16. CLINICAL RESEARCHMulticenter Clinical Trial Laboratory certification • Sponsor requires documentation of certification for Clinical Laboratory (not a problem at U Va) – obtain certificate from Clinical Pathology

17. CLINICAL RESEARCHMulticenter Clinical Trial Study Coodinator • Full time: expensive, not always practical for a new investigator • Do you have the time to attend to details, paperwork?

18. CLINICAL RESEARCHRewards Cutting edge research; new treatments: examples: FDA approval: • GHRH physiology; treatment GH deficiency • 3 dopamine agonists for prolactin producing pituitary tumors • 2 somatostatin analogs for acromegaly • GH receptor antagonist for acromegaly • GH replacement in adults; depot GH • Transdermal testosterone, 2 drugs

19. CLINICAL RESEARCHSummary • Advances clinical science (human beings: the ultimate in “translational research”) • Potential for new medical treatments, procedures • Requires a great deal of paperwork, but worth it!

20. EFFECT OF OCTREOTIDE OR SOMAVERT 2100 Somavert (10 - 35 mg/day) 1800 Octreotide + Bromocriptine 1500 1200 IGF-I (ng/ml) 900 Gamma Knife TSS Radiosurgery 600 Normal Range 300 0 Jul-93 Jul-94 Jul-95 Jul-96 Jul-97 Jul-98 Jul-99 Jan-94 Jan-95 Jan-96 Jan-97 Jan-98 Jan-99 Jan-00 Time GDM

21. Sugar – My New Bulldog