Protocols and GCP - ICSSC

1 Good clinical Practice1 Protocols and GCPP rotocols and GCPGood clinical Practice2 Purpose of ProtocolPurpose of ProtocolClear and complete description of rationale, methods, and analysisGives us the details before research beginsAllows us to decide if the research isethical, relevant, and clinical Practice3 General Information General Information ICH E6: Section E6: Section title, identifying number, version numberand dateGood clinical Practice4 General InformationGeneral InformationICH E6: Section E6: Section , address of the sponsorSponsor s medical expert for the studyGood clinical Practice5 Background Information Background Information ICH E6: Section E6: Section with protocol , GCP, and regulatory requirementsGood clinical Practice6 General InformationGeneral InformationICH E6: Section E6: Section Address, telephone of study site Include names and addresses of labs, data management, statistician, etc.

2 Investigator responsible for the studyGood clinical Practice7 Background InformationBackground InformationICH E6: Section E6: Section of findings from nonclinical and clinical studiesBrief description of study product or interventionPotential risks and benefits to participantsWhy is study needed?Good clinical Practice8 Trial Objectives and Purpose Trial Objectives and Purpose ICH E6: Section E6: Section OBJECTIVES AND OUTCOMES MEASURESP rimary ObjectiveTo define levels of serotype neutralizing-specific Abs associated with protective immunity against symptomatic dengue. Secondary Objective To delineate risk factors contributing to the pathogenesis of DHF in infants. Primary Outcome Measure:Neutralizing Ab titers in blood samples collected before DV infection, and predicted neutralizing Ab titers at the time of illness will be correlated with disease severity and peak viremia levels.

3 Ab titers at which infants developed symptomatic dengue will be determined. Study objectivesSpecific, measurableFewer the betterLinked to endpoints/outcomesGood clinical Practice9 Trial DesignTrial DesignICH E6: Section E6: Section ICH GCP, the trial design section of the protocol should include: Statement of primary and secondary endpoints consistent throughout protocol Type/design of study ( cohort, case-control, etc.) Measures to minimize/avoid bias ( , participant selection, randomization) Schematic diagram of study designGood clinical Practice10 Trial Design Trial Design ICH E6: Section E6: Section of subject participation; time to complete specimen collectionStopping rules and discontinuation criteriaInvestigational product accountability proceduresInvestigational product dosage, packaging, to be recorded directly on CRF to be considered sourceGood clinical Practice11 Selection and Withdrawal of Selection and Withdrawal of ParticipantsParticipantsICH E6 Section E6 Section for: Inclusion Exclusion Withdrawal Who decides?

4 Replacement?Good clinical Practice12 Treatment of Subjects Treatment of Subjects ICH E6: Section E6: Section what procedures done with participants, , labs, interviews, environmental samplesDose, dosing schedule, routes of administration, treatment periodsConcomitant medicationsMonitoring complianceGood clinical Practice13 Assessment of Efficacy and Safety Assessment of Efficacy and Safety ICH E6: Section and E6: Section and parameters How and when assessedSafety parameters How and when adverse events assessed and reported Length of follow-up after adverse eventGood clinical Practice14 WhatWhatisisan Adverse an Adverse EventEvent(AE)?(AE)? Any unfavorable and unintended sign, Any unfavorable and unintended sign, symptom or disease, temporally symptom or disease, temporally associated with the use of a medicinal associated with the use of a medicinal product, drug device, or product, drug device, or administration administration of a medical procedureof a medical procedure Consult with sponsor regarding Consult with sponsor regarding requirements for AE reportingrequirements for AE reportingCCPGood clinical Practice15 State explicitly in the protocol :State explicitly in the protocol .

5 Known risks and possible Known risks and possible AEsAEsIf assessing preIf assessing pre--existing conditions and existing conditions and concomitant medsconcomitant medsTimeline for detecting and reporting Timeline for detecting and reporting AEsAEsProcedure for reporting pregnancyProcedure for reporting pregnancyAbnormal lab findingsAbnormal lab findingsHow intensity and relationship assessedHow intensity and relationship assessed if using if using Toxicity Table or other resourcesToxicity Table or other resourcesHalting rulesHalting rules ICH E6: Section E6: Section clinical Practice16 StatisticsStatisticsICH E6: Section E6: Section section should include: Description of statistical methods for endpoints/outcome measures The number of subjects (and justification) Level of significance used Termination criteria Procedure of accounting for missing, unused and spurious data Plan for reporting deviations from statistical plan Who will be included in analysis--All enrolled subjects?

6 Only those who completed all procedures? Good clinical Practice17 Access to Source Data/DocumentsAccess to Source Data/DocumentsICH E6: Section E6: Section Each site will allow authorized representatives of sponsoraccess to: Participant recordsData filesRegulatory filesPharmacy and laboratory recordsRelevant medical/hospital records For purposes of monitoring, audits, IRB reviewsGood clinical Practice18 Participant ConfidentialityParticipant ConfidentialityIn the Informed Consent Form State procedures for protecting confidentiality, data security procedures, record storageGood clinical Practice19 Data Handling and Recordkeeping Data Handling and Recordkeeping ICH E6: Sections E6: Sections must maintain documentation Ensure data are AccurateCompleteConsistent/reliable Indicate roles of staff for collecting, recording, analysis, reportingMethods of data captureSchedule of reports, analysisGood clinical Practice20 Other Sections Other Sections ICH E6: Sections E6: Sections Control and Quality AssuranceEthics IRB reviewConsent process minors, low literacy, other vulnerable populationsConfidentialityFinancing and Insurance -usually in separate documentPublication PolicyGood clinical Practice21 protocol ComplianceProtocol ComplianceICH E6: Section E6: Section change in procedures, except.

7 Through anapproved amendment Approval by sponsor Approval by IRB/IEC Approval by regulatory authority, if requiredTo eliminate an immediate hazard to a participantIf change involves administrative or logistical aspects of the study, such as phone numberGood clinical Practice22 protocol DeviationsProtocol DeviationsAny noncompliance with the protocol , GCP, or protocol -specific Manual of ProceduresrequirementsNon-compliance by participant, investigator or staffReport to sponsor per its requirementsReport to IRB/IEC per its requirementsCopy in participant and regulatory filesGood clinical Practice23 Examples of protocol Examples of protocol DeviationsDeviationsAssessments or procedures not done or not completed as requiredStudy procedure errors ( , wrong dose, wrong timeframe, missed visit)Lab procedure errors ( , used wrong type of tube)Failure to use the current approved version of the informed consentConsent form is missing, or consent form was not signed appropriatelyIRB violations ( , failure to conduct continuing review)Good clinical Practice24 SummarySummaryConsult with sponsor Review GCP E6: Section 6 for protocol requirementsIt takes a team to write a protocol clinician, statistician, data manager, it relevant, ethical and feasible, please!

8 Good clinical Practice25 ItIt s a tough job!s a tough job!DMID Specimen protocol Template: Minimal Risk Version 29 September 2004 _____ _____ PREFACE This document is the DMID protocol template, which is required for DMID-sponsored clinical studies that pose only minimal risk to study subjects. Minimal risk is defined by 45 Code of Federal Regulations (CFR) (i) as follows: Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. Refer to: # Categories of research that are minimal risk are defined by OHRP guidelines. Refer to: Note that instructions and explanatory text are indicated by italics and should be replaced in your protocol document with appropriate protocol -specific text.

9 Section headings and template text formatted in regular type should be included in your protocol document as provided in the template. The Principal Investigator (PI) must attach all explanatory and appended materials (including, but not limited to, surveys, consent forms, interview scripts, and recruitment flyers/brochures) referred to in the protocol . Refer questions regarding use of this protocol template to the appropriate DMID protocol Champion or clinical Affairs Specialist. DMID Specimen protocol Template: Minimal Risk Version 29 September 2004 _____ _____ TITLE *DMID protocol Number: *( protocol number required protocol Champion must complete attached form) Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) DMID Funding Mechanism: Principal Investigator: *DMID protocol Champion: *( protocol Champion must complete attached form to generate protocol Number) Draft or Version Number: (see DMID SOP for assigning version #s) Day Month Year (Write out the month and use international date format, , 23 January 2004) This template is adapted from the ICH guidance document E6 (Good clinical Practices), Section 6.

10 DMID Specimen protocol Template: Minimal Risk Version 29 September 2004 _____ _____ i Statement of Compliance Provide a statement that the clinical study will be conducted in compliance with the protocol , GCP and the applicable regulatory requirements. An example is provided below: The study will be carried out in accordance with Good clinical Practice (GCP) as required by the following [use applicable regulations depending on study location and sponsor requirements; samples follow]: Code of Federal Regulations applicable to clinical studies (45 CFR 46) ICH GCP E6 Completion of Human Subjects Protection Training NIH clinical Terms of Award Refer to: #46. DMID Specimen protocol Template: Minimal Risk Version 29 September 2004 _____ _____ ii SIGNATURE PAGE The signature below constitutes the approval of this protocol and the attachments, and provides the necessary assurances that this trial will be conducted according to all stipulations of the protocol , including all statements regarding confidentiality, and according to local legal and regulatory requirements and applicable US federal regulations and ICH guidelines.