Jasper Ogwal-Okeng

Gulu University Research Workshop 3rd-6th March 08

Clinical TrialsEvaluation of a Product for Clinical Effects

Safety and EffectivenessProduct can be

DrugsVaccines

Phases of Clinical TrialsPhase I: Healthy volunteersPhase IIa: Early phase IIPhase IIb: Late phase IIPhase III: RCT, blindedPhase IV: Pharmacovigilance

Phase IFollows successful pharmacological and

toxicological studies in animalsHealthy volunteersSafety and pharmacokinetic data obtained

(not efficacy-since no symptoms)Start with 1/5th or 1/10th maximum tolerated

dose in the most sensitive animal speciesPlacebo and double-blinded

Phase II StudiesFirst administered to patients

Phase II a (Early phase II)Potential benefits and side effectsEstablish dose range for phase IIb

Phase IIb (Late phase II)Establish efficacy in specific diseaseCompare efficacy and side effects with other

drugs for same conditions

Phase III studiesRandomized, controlled, double-blind edSufficient 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 IVAfter drug obtained marketing licenseMonitored for

Rare side effectsChronic toxicity e.g. cancer after many people-

years of usePreviously unknown interactionsPotential new therapeutic useDose 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 EVALUATIONProcedures for submissionProcedures for Review and ApprovalInstitutional Review BoardsAmendments to Trial ProtocolInspection/Audit by NDAReports and Final Review

Procedure for Application submissionTo Executive Secretary/Registrar NDAFee and structureClinical Trial application formDocuments accompanying application form

(Appendices 1-17)

FEE/STRUCTURETYPE 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

US $ 4000

Phase I, Phase II or Phase III patient /animal trial with a known product

US $ 3000

Phase IV trial US $ 200

Protocol Amendment US $ 100

TRIALS OF TRADITIONAL /COMPLEMENTARY MEDICINESTraditional medicines US $ 500

Complementary medicines US $ 2000

Review and Approval of ApplicationsCompleteness-form, document and feeApplication reference numberSupplementary Data and updatesExpert Review (appointed by NDA)Approval by NDA’s Clinical Trials Committee

(CTC)Approval communicated in writingPost Trial Review

Institutional Review BoardsEstablished in the institution where research

is doneEnsures safety, integrity and human rights

issuesCTC of NDA oversees all IRBsNDA approves application after IRB and

NCST approvals

Amendments to Trial ProtocolMay be partial or complete.Urgent-Change and inform IRB, NCST,NDAOtherwise resubmit to NDA and wait decision

Inspection/Audit by NDATo verify monitoring and audit of protocolFacilitiesResearch staffCompliance with protocolSerious Adverse Events being reported

Reports and Final ReviewReporting of Serious Adverse EventsInterim and Final Trial ReportsDissemination and PublicationArchiving

CLINICAL TRIAL LICENSE (CTL)Approval for importation/manufacture of CT

commodities given after CT approvalProducts that require CTLProcedures for Application for CTLConditions for CTLImportation and Release of Investigational

Product (IP)Documentation for IP Release

Products that Require CTLUnregistered products, including placebosRegistered

Used/assembled in different form from approved form

Used for unapproved indicationUsed to gain further information about

approved useLocal product manufactured for Clinical Trial

Application Procedures for CTLWho to apply:

Principal InvestigatorSponsor (authorized person from a

pharmaceutical company)

AttachmentsFormat for Clinical Trial ProtocolInvestigator’s brochureGuide for labeling clinical trial medicinesLetter of authorizationClinical Trial application formFormat for clinical trial reportsDeclaration by InvestigatorsCheck list for required documentation

HOW IT WAS - MAY 2004- GULU HOSPITAL

HOW IT IS – OCTOBER 2004 - FACULTY OF MEDICINE