1. Jasper Ogwal-Okeng Gulu University Research Workshop 3 rd -6 th March 08

2. Clinical Trials Evaluation of a Product for Clinical Effects Safety and Effectiveness Product can be Drugs Vaccines

3. Phases of Clinical Trials Phase I: Healthy volunteers Phase IIa: Early phase II Phase IIb: Late phase II Phase III: RCT, blinded Phase IV: Pharmacovigilance

4. Phase I Follows successful pharmacological and toxicological studies in animals Healthy volunteers Safety and pharmacokinetic data obtained (not efficacy-since no symptoms) Start with 1/5 th or 1/10 th maximum tolerated dose in the most sensitive animal species Placebo and double-blinded

5. Phase II Studies First administered to patients Phase II a (Early phase II) Potential benefits and side effects Establish dose range for phase IIb Phase IIb (Late phase II) Establish efficacy in specific disease Compare efficacy and side effects with other drugs for same conditions

6. Phase III studies Randomized, controlled, double-blind ed Sufficient sample size for statistical evaluation of efficacy and safety. Successful phase III trial leads to New Drug Submission (NDS) NDS requests permission to market new drug

7. Phase IV After drug obtained marketing license Monitored for Rare side effects Chronic toxicity e.g. cancer after many people- years of use Previously unknown interactions Potential new therapeutic use Dose modifications

8. Guidelines for Clinical Ttrials in Uganda All medicines used in Uganda should be registered with National Drug Authority (NDA) Written approval of NDA needed for clinical of drugs (registered/unregistered) used in Uganda Guidelines gives procedures of application for clinical Trials

9. APPLICATION SUBMISSION, REVIEW AND EVALUATION Procedures for submission Procedures for Review and Approval Institutional Review Boards Amendments to Trial Protocol Inspection/Audit by NDA Reports and Final Review

10. Procedure for Application submission To Executive Secretary/Registrar NDA Fee and structure Clinical Trial application form Documents accompanying application form (Appendices 1-17)

11. FEE/STRUCTURE TYPE OF TRIALFEES HUMAN AND VETERINARY TRIAL Phase I Healthy Volunteer trialUS $ 500 Phase I, Phase II or Phase III patient/animal trial with an unknown product US $ 4000 Phase I, Phase II or Phase III patient /animal trial with a known product US $ 3000 Phase IV trialUS $ 200 Protocol AmendmentUS $ 100 TRIALS OF TRADITIONAL /COMPLEMENTARY MEDICINES Traditional medicinesUS $ 500 Complementary medicinesUS $ 2000

12. Review and Approval of Applications Completeness-form, document and fee Application reference number Supplementary Data and updates Expert Review (appointed by NDA) Approval by NDA’s Clinical Trials Committee (CTC) Approval communicated in writing Post Trial Review

13. Institutional Review Boards Established in the institution where research is done Ensures safety, integrity and human rights issues CTC of NDA oversees all IRBs NDA approves application after IRB and NCST approvals

14. Amendments to Trial Protocol May be partial or complete. Urgent-Change and inform IRB, NCST,NDA Otherwise resubmit to NDA and wait decision

15. Inspection/Audit by NDA To verify monitoring and audit of protocol Facilities Research staff Compliance with protocol Serious Adverse Events being reported

16. Reports and Final Review Reporting of Serious Adverse Events Interim and Final Trial Reports Dissemination and Publication Archiving

17. CLINICAL TRIAL LICENSE (CTL) Approval for importation/manufacture of CT commodities given after CT approval Products that require CTL Procedures for Application for CTL Conditions for CTL Importation and Release of Investigational Product (IP) Documentation for IP Release

18. Products that Require CTL Unregistered products, including placebos Registered Used/assembled in different form from approved form Used for unapproved indication Used to gain further information about approved use Local product manufactured for Clinical Trial

19. Application Procedures for CTL Who to apply: Principal Investigator Sponsor (authorized person from a pharmaceutical company)

20. Attachments Format for Clinical Trial Protocol Investigator’s brochure Guide for labeling clinical trial medicines Letter of authorization Clinical Trial application form Format for clinical trial reports Declaration by Investigators Check list for required documentation

21. HOW IT WAS - MAY 2004- GULU HOSPITAL

22. HOW IT IS – OCTOBER 2004 - FACULTY OF MEDICINE

23. Good Luck