Guidelines for Clinical Trials in Uganda Jasper OgwalOkeng

Guidelines for Clinical Trials in Uganda Jasper Ogwal-Okeng Gulu University Research Workshop 3 rd-6 th March 08

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

HOW IT WAS - MAY 2004 - GULU HOSPITAL

HOW IT IS – OCTOBER 2004 - FACULTY OF MEDICINE

Good Luck