protocol understanding_ clinical data management_katalysthls

PowerPoint Presentation

1Protocol Understanding2/23/2017

Clinical Data Management (CDM)Katalyst Healthcares & Life Sciences

Icons Used:

QuestionsDemonstration

Hands on ExerciseCoding Standards

A Welcome BreakTools

ReferenceTest Your Understanding

Contacts

2/23/20172

The protocol contains a study plan on which the clinical trial is based.

Protocol is designed in such a way that it safeguards the health of the participants (while limiting their financial liability) and also answer specific research questions

Protocol lays out who, what, why, when, where, how about the clinical trial

It safeguards clinical trial integrityProtocol Understanding: Overview3Katalyst Healthcares & Life Sciences

After completing this chapter you will be able to:Understand protocol documentUnderstand the contents of a protocolUnderstand the importance of protocol in clinical trials

Objectives:4Katalyst Healthcares & Life Sciences

4

Protocol is a set of rules. Consider that you are driving a car. You have to follow some set of rules while you are driving. Why are traffic rules required? These traffic rules ensures that the transportation occurs in smooth and safe way. Similarly in Clinical trials, the protocols were set up so that the transportation of clinical data across study teams is smooth and safe

CDISC is creating a standard called the Protocol Representation Model(PRM), which identifies, defines and describes over 300 common protocol elements and maps those elements to elements within the BRIDG model. The PRM model is intended as a standard to be used in designing a study, selecting investigative sites, developing data collection tools, and describing an analysis plan and study proceduresDo You Know:5Katalyst Healthcares & Life Sciences

CDISC: Clinical data interchange standards consortiumThe Clinical Data Interchange Standards Consortium (CDISC) is an open, multidisciplinary, neutral, non-profit standards developing organization (SDO) that has been working through productive, consensus-based collaborative teams to develop global standards and innovations to streamline medical research and ensure a link with healthcare

BRIDG: Biomedical Research Integrated Domain Group CDISC BRIDG model is a unifying model of the domain of clinical research and research studies. It defines basic elements such as investigator, subject, study, intervention. It is used to keep all standards consistent. 5

Amending the protocol immediately after an issue is discovered contributes significantly to patient safety and overall success of the study

The following practices should be followed during the design of electronic CRFs:The protocol should determine what data should be collected on the CRF All data must be collected on the CRF if specified in the protocol

Do You Know:6Katalyst Healthcares & Life Sciences

A Clinical Trial Protocol is a document that describes the objective(s), design, methodology, statistical considerations, and organization of a clinical trial. - ICH-GCP Guidelines

Protocol Definition:7

Katalyst Healthcares & Life Sciences

The protocol gives the background and reason the trial is being conducted

The protocol contains a study plan on which the clinical trial is based. The plan is designed to safeguard the health of the participants (while limiting their financial liability) as well as answer specific research questions

The protocol describes, among other things, what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study

While in a clinical trial, study participants are seen regularly by the research staff (usually medical doctors and/or nurses) to monitor their health and to determine the safety and effectiveness of the treatment(s) they are receiving

Protocol Overview:8Katalyst Healthcares & Life Sciences

Protocol - Cover Page:9

Protocol Title: A randomized double blind placebo controlled study to investigate the safety of XYZ in healthy adult volunteers

Protocol Number: ABCD0001 Protocol Date: 10 October 2011 Study Phase: I Project Leader: Jill J JackProtocol Author(s): A Fernandes PhD B Neil PhDC Frank PhD

Confidentiality Agreement INVESTIGATOR: A Fernandes TT Hospital1st Floor, Ward 1A, Delhi, India SPONSOR: ABCL LtdThe International Centre Kensington SEZ, PO Box X11, Mumbai, India This document is a confidential communication of ABCL Ltd. Acceptance of this document constitutes the agreement by the recipient that no unpublished information contained within will be published or disclosed without prior written approval, except that this document may be disclosed to the appropriate Ethics Committee and Regulatory Authority under the condition that they are requested to keep it confidential

Protocol Content 10Katalyst Healthcares & Life Sciences

Background:Name and/or identity (i.e. chemical composition) of the investigational drug product(s) and the disease or condition for which the investigational drug product(s) is (are) being evaluatedCurrent status of the disease or condition for which the investigational drug(s) is (are) being evaluated; to include current problems or deficiencies that warrant an evaluation of the investigational drug

Rationale:Reason(s) why investigational drug(s) will be safe and effective for the clinical indicationDescription of, and justification for, the proposed route of administration, dosage, dosage regimen, and duration of dosing of the investigational drug(s)Nature of the individuals (e.g., age range, sex, disease state or underlying condition) who will be included in the proposed clinical evaluation of the investigational drug(s)If the investigational drug(s) has (have) been withdrawn from research or marketing in any country for any reason related to its safety or effectiveness

1. Introduction:11Katalyst Healthcares & Life Sciences

2. Clinical Study Objectives:12This section includes: 1. Primary objective:Address the primary objective and specific aim(s) of the proposed clinical evaluation of the investigational drug(s)Example: To lower the blood glucose level by 20 units 2. Secondary objectives:Address, if applicable, secondary objective(s) and specific aim(s) of the proposed clinical evaluation of the investigational drug(s)Example: To improve the quality of life 3. Endpoints: These are outcome measures used to address the objectives of a clinical trial.The primary endpoint is the most important outcome and is used to assess the primary objective of a trial Example: The variable used to compare the effect difference of two treatment groups).


The scientific integrity of the trial and the credibility of the data from the trial depend substantially on the trial design. This includes:

A specific statement of the primary endpoints and the secondary endpoints, if any, to be measured during the trialA description of the type/design of trial to be conducted (e.g. double-blind, placebo-controlled, parallel design) and a schematic diagram of trial design, procedures and stagesA description of the measures taken to minimize/avoid bias, including:(a) Randomization (b) BlindingA description of the trial treatment(s) and the dosage and dosage regimen of the investigational product(s). Also include a description of the dosage form, packaging, and labeling of the investigational product(s).The expected duration of subject participation, and a description of the sequence and duration of all trial periods, including follow-up, if any

3. Study Design:13Katalyst Healthcares & Life Sciences

A description of the stopping rules or discontinuation criteria for individual subjects, parts of trial and entire trial

Accountability procedures for the investigational product(s), including the placebo(s) and comparator(s), if any

Maintenance of trial treatment randomization codes and procedures for breaking codes

The identification of any data to be recorded directly on the CRFs (i.e. no prior written or electronic record of data), and to be considered to be source data3. Study Design contd..14


3. Study Design contd:15

Subject inclusion criteriaInclusion criteria are characteristics that the prospective subjects must have if they are to be included in the study

Example: 1. Study subjects must meet age (in years) and gender (men and women) criteria of the study protocol.2. Study subjects must meet disease criteria as specified by the study protocol.

Subject exclusion criteriaExclusion criteria are those characteristics that disqualify prospective subjects from inclusion in the study.

Example: 1. Study subjects must not have a medical history of sensitivity, intolerance, or toxicity to the investigational product, or agents similar to the investigational product.2. Study subjects must not have donated blood two months prior to study entry, and must not donate blood after study entry until at least 30 days after the study subject has completed the study.4. Subject Selection:16Katalyst Healthcares & Life Sciences

3. Subject withdrawal criteria (i.e. terminating investigational product treatment/trial treatment) and procedures specifying:

When and how to withdraw subjects from the trial/ investigational product treatmentThe type and timing of the data to be collected for withdrawn subjectsWhether and how subjects are to be replacedThe follow-up for subjects withdrawn from investigational product treatment/trial treatment

4. Subject Selection:17Katalyst Healthcares & Life Sciences

The treatment(s) to be administered, including the name(s) of all the product(s), the dose(s), the dosing schedule(s), the route/mode(s) of administration, and the treatment period(s), including the follow-up period(s) for subjects for each investigational product treatment/trial treatment group/arm of the trialMedication(s)/treatment(s) permitted (including rescue medication) and not permitted before and/or during the trialProcedures for monitoring subject complianceWithdrawal of subjects due to non-compliance/ adherenceStudy drug supplies:Formulation and packagingPreparing and dispensingDrug administrationStudy drug storage and accountabilityDescription of Concomitant Medications and Rescue Medications.5. Study Drug(s):18


18

Screening procedures : Description of the procedures performed at subject screening to verify subject eligibility for study participation

Study drug procedures : Description of the procedures performed for, and in association with, the administration of the study drug(s)

3. Follow-up procedures (only if follow-up procedures will be performed)Description of follow-up procedures that will be performed after the subject completes the study drug administration proceduresSchedule of activities (Study Table)A table that summarizes the clinical protocol procedures; to include the procedures that will be performed at screening, during the study drug administration, and at follow-up (if applicable) to the study drug administration

6. Research Study Procedures:19Katalyst Healthcares & Life Sciences

Assessment of Safety :

Specification of safety parameters

The methods and timing for assessing, recording, and analyzing safety parameters

Procedures for eliciting reports of and for recording and reporting adverse event and inter-current illnesses

The type and duration of the follow-up of subjects after adverse events 7. Safety and Efficacy Assessments:20


Assessment of Efficacy :

Specification of the efficacy parameters

Methods and timing for assessing, recording, and analyzing of efficacy parameters

7. Safety and Efficacy Assessments contd..21

Adverse event definitions

Recording/Reporting requirements :Eliciting adverse event informationRecording requirements

Reporting of adverse reactions :Reporting of adverse reactions to the FDAReporting adverse events to the responsible IRB

Withdrawal of subjects due to adverse events

8. Adverse Event Reporting:22

A description of the statistical methods to be employed, including timing of any planned interim analysisThe number of subjects planned to be enrolled. In multicenter trials, the numbers of enrolled subjects projected for each trial site should be specified. Reason for choice of sample size, including reflections on (or calculations of) the power of the trial and clinical justificationThe level of significance to be usedCriteria for the termination of the trialProcedure for accounting for missing, unused, and spurious dataProcedures for reporting any deviation(s) from the original statistical plan (any deviation(s) from the original statistical plan should be described and justified in protocol and/or in the final report, as appropriate)The selection of subjects to be included in the analyses (e.g. all randomized subjects, all dosed subjects, all eligible subjects, evaluable subjects)

9. Statistical Methods/Data Analysis:23

23

Description of nature and timing of the quality control/quality assurance reviews (i.e., independent of the previously described monitoring activities) that will be undertaken by the Sponsor-Investigator to ensure appropriate conduct of the clinical research study and quality and completeness of the accrued study data. I.e., describe the data and safety monitoring plan for the proposed clinical research study.

10. Quality Control and Quality Assurance:24Katalyst Healthcares & Life Sciences

Data recording/Case Report Forms : A Case Report Form (CRF) should be completed for each subject enrolled into the clinical study. The Sponsor-Investigator will review, approve and sign/date each completed CRF; the Sponsor-Investigators signature serving as attestation of the Sponsor-Investigators responsibility for ensuring that all clinical and laboratory data entered on the CRF are complete, accurate and authentic.

Record maintenance and retention : The Sponsor-Investigator will maintain records in accordance with Good Clinical Practice guidelines.11. Data Handling and Record-Keeping:25Katalyst Healthcares & Life Sciences

The sponsor should ensure that it is specified in the protocol or other written agreement that the investigator(s)/institution(s) will permit trial-related monitoring, audits, IRB/IEC review, and regulatory inspection(s), providing direct access to source data/documents.

25

Institutional Review Board (IRB) approval

Ethical and scientific conduct of the clinical research study

Subject informed consent

12. Ethics:26Katalyst Healthcares & Life Sciences

Discontinuation of individual research subjects : Addresses any discontinuation criteria or stopping rules for individual research subjects that were not addressed previously under section 5.1.1 (Withdrawal of subjects due to non-compliance/adherence) or section 8.4 (Withdrawal of subjects due to adverse events) of the clinical protocol.

Sponsor-Investigator discontinuation of the clinical research study : Describes the discontinuation criteria or stopping rules for parts of the clinical research study, if applicable, or for the entire clinical research study.13. Study Discontinuation Criteria:27Katalyst Healthcares & Life Sciences

Lets see how does a protocol look like :

Lets discuss:28


Define Protocol?

Which section of protocol describes procedures for monitoring subject compliance ?

Fill in the blank: The Sponsor-Investigator will maintain records in accordance with ________________

Procedures for reporting any deviation(s) from the original statistical plan described and justified in __________and/or in the final report, as appropriate)

Test Your Understanding:29


Answers: 1. A Clinical Trial Protocol is a document that describes the objective(s), design, methodology, statistical considerations, and organization of a clinical trial 2. Section 5 Study drug3. Good Clinical Practice guidelines4. protocol5.

29

In this session the following topics were covered:

Introduction to Clinical study protocol Contents of a protocolImportance of protocol in clinical trials

Summary:

30Katalyst Healthcares & Life Sciences

You have successfully completed - Protocol Understanding

Summary:31Katalyst Healthcares & Life Sciences

32

Thank You&QuestionsContact:Katalyst Healthcares & Life SciencesSouth Plainfield, NJ, USA 07080.E-Mail: [email protected]

TICIPS (The International Center for Indigenous Phytotherapy Studies)

Clinical Study Protocol No: TICIPS001 Protocol Date: 10 October 2003

Protocol Version 1: 10 October 2003. Corrected 19 Feb 2004 1

Protocol Cover Page

Protocol Title: A randomized double blind placebo controlled study to investigate

the safety of Sutherlandia frutescens (subspecies microphylla) in

healthy adult volunteers.

Protocol Number: TICIPS001

Protocol Date: 10 October 2003

Study Phase: I

Project Leader: J A Syce

Protocol Author(s): J A Syce PhD

H Nell MBChB

G Fatti MBChB

Confidentiality Agreement

This document is a confidential communication of TICIPS. Acceptance of this document constitutes the

agreement by the recipient that no unpublished information contained within will be published or

disclosed without prior written approval, except that this document may be disclosed to the appropriate

Ethics Committee and Regulatory Authority under the condition that they are requested to keep it

confidential.

SPONSOR: TICIPS The International Centre for

Indigenous Phyotherapy Studies

South African Herbal Science and

Medicine Institute, University of the

Western Cape (UWC), Private Bag

X17, Bellville, South Africa.

INVESTIGATOR: Dr H Nell,

Tijger Trial Centre (TTC),

1st Floor, Ward 1A,

Mike Pienaar Boulevard, Karl

Bremer Hospital,

Bellville 7531,

South Africa.




TABLE OF CONTENTS PAGE

LIST OF ABBREVIATIONS AND DEFINITIONS 4

STUDY CONTACT LIST 6

PROTOCOL SYNOPSIS 7

1 INTRODUCTION 9

1.1 Background 9 1.2 Study Rationale 10

2 STUDY OBJECTIVES 10

3 STUDY PLAN AND PROCEDURES 10

3.1 Study design 10 3.1.1 Scheduled clinic visits 11 3.1.2 Visits and assessments 11 3.2 Study population 11 3.2.1 Inclusion criteria 11 3.2.2 Exclusion criteria 12 3.2.3 Justification for inclusion and exclusion criteria 12 3.2.4 Criteria for discontinuation 12 3.3 Investigational Products and Treatments 12 3.3.1 Treatment Schedule 12 3.3.2 Randomization 13 3.3.3 Identity of Study Products 13 3.3.4 Storage and Accountability 13 3.3.5 Allowed medication 13 3.4.1 Compliance 13

4 STUDY MEASUREMENTS AND ENDPOINTS 14

4.1 Primary Safety Endpoints 14 4.2 Secondary Safety Endpoint 14 4.3 Measurements at each visit 14 4.4 Specific detail on measurements 15 4.4.1 Adverse Events 15 4.4.2 12-Lead ECG 16 4.4.3 Laboratory Investigations 16 4.4.3.1 Haematology 16 4.4.3.2 Clinical Chemistry 16 4.4.3.3 Blood levels of active constituents 16 4.5 Measurements recorded daily in diary 17

5 STATISTICAL METHODS 17

5.1 Determination of sample size 17 5.2 Statistical analysis 5.3 Changes to the protocol 17




6 ETHICS 18

6.1 Ethics review 18 6.2 Ethical conduct of the study 18 6.3 Subject information and consent 18 6.4 Subject data protection 18 6.5 Insurance and Indemnity 18

7 DATA QUALITY ASSURANCE 18

8 STUDY TIMETABLE AND TERMINATION 19

9 REFERENCES 19

10 APPENDICES

10.1 Declaration of Helsinki 21 10.2 Sample written informed consent 25 10.3 Diary for treatment period 39 10.4 Ideal Body Mass Tables 43 10.4.1 Sutherlandia Literature 44




LIST OF ABBREVIATIONS AND DEFINITIONS

The following abbreviations and specialist terms are used in this study protocol:

Abbreviation Explanation

AE Adverse Event

ALP Alkaline phosphatase

ALT Alanine aminotransferase

AST Aspartate aminotransferase

b.i.d bis in die = twice daily

CD4+ count of CD4 expressing helper T lymphocytes

CD8+ count of CD8 expressing cytotoxic T lymphocytes

CK creatine phosphokinase

CRF Case Report Form

ECG Electrocardiogram

GABA Gamma aminobutyric acid

GCP Good Clinical Practice

GGT gamma glutamyl transpeptidase

Hb Haemoglobin

Hct Haematocrit

HDL-C High Density Lipoprotein cholesterol

HPLC High performance liquid chromatography

ICH International Conference of Harmonisation

IEC Independent Ethics Committee

IRB Independent Review Board

LCMS Liquid chromatography linked mass spectrometry

LDH Lactate dehydrogenase

LDL-C Low Density Lipoprotein -cholesterol

MS Mass spectrometry

MCH Mean corpuscular haemoglobin

MCHC Mean corpuscular haemoglobin concentration

MCV Mean corpuscular volume

ml milliliter

MRC Medical Research Council

OHRP Office of Human Research Protections (of Federal Department of

Health & Human Services, USA)

RDW Red cell distribution width

RBC Red Blood Cells

SAE Serious Adverse Event

SG Specific gravity

SEM Standard error of the mean

SLE Systemic lupus erythematosus

T3 Triiodothyronine

T4 Thyroxine

TICIPS The International Centre for Indigenous Phytotherapy Studies

TSH Thyroid-stimulating hormone

TTC Tijger Trial Centre

UWC University of the Western Cape

WBC White blood cells

Definitions




Herbal Medicines: Mainly whole, fragmented or cut plants, part of plants in an unprocessed state, usually in dried

form, but sometimes fresh. Herbal drugs are precisely defined by the botanical scientific name according to the

binomical system (genus, species, variety).

African traditional medicine: The total body of knowledge and techniques for the preparation and use of substances,

measures and practices that are based on the socio-cultural and religious bedrock of African communities, are

founded on personal experience and observations handed down from generation to generation, either verbally or in

writing, and are used for the diagnosis, prevention or elimination of imbalances in physical, mental or social well-

being.




STUDY CONTACT LIST For questions regarding the conduct of this study, please contact:

Project Leader: James A Syce, M Pharm, PhD

E-mail: [email protected]

Telephone: +27 21 959 2192

Mobile: 082 202 3315

Telefax: +27 21 959 1324

Clinical Trial Manager: Haylene Nell, MBChB, BSc (Honns-Pharmacology)

(Clinical investigator) E-mail: [email protected] or [email protected]

Telephone: +27 21 918 1399/ 1272

Mobile: 083 448 1456

Telefax: +27 21 918 1468

For reporting a serious adverse event, please contact:

Clinical Trial Manager: Haylene Nell, MBChB, BSc (Honns-Pharmacology)

E-mail: [email protected] or [email protected]

Telephone: +27 21 918 1399/ 1272

Mobile: 083 448 1456

Telefax: +27 21 918 1468

For questions regarding data quality assurance, please contact:

Independent Study Monitor: Ms Laurie Ben-yair, CRA

On Q Consulting, CC.

E-mail: [email protected]

Telephone: +27 21 556 1524

Mobile: 083 457 6050

Telephone: +27 21 556 1524

mailto:[email protected]:[email protected]:[email protected]:[email protected]




PROTOCOL SYNOPSIS

TITLE

A randomized double blind placebo controlled study to investigate the safety of Sutherlandia frutescens (subspecies microphylla) in healthy adult volunteers.

Investigational site: TTC, First Floor Ward 1A, Karl Bremer Hospital, Bellville, Cape Town, South Africa (& UWC, Health Centre, Bellville, Cape Town, South Africa)

Investigators: Prof. James Syce, Dr. Haylene Nell, Prof. Pierre. Mugabo, and Prof. Quinton Johnson

Sponsor: The International Centre for Indigenous Phytotherapy Studies (TICIPS)

Representatives: Prof. Quinton Johnson

Study number: TICIPS001

Final Protocol: Oct 2003 / 19 Feb 2004 Clean File: August 2004/ November 2004

Ethics Approval: Nov 2003 / 10 Mar 2004 MCC approval: 20 Jul 2004

Statistical analysis: August 2004 / November 2004

Clinical Phase: Mar to Jul 2004/ Aug Nov 2004

Study Report: September 2004/ November 2004

OBJECTIVES:

To investigate the safety of Sutherlandia frutescens (subsp. Microphylla) capsules in healthy adult volunteers by assessing, liver, kidney, muscle, metabolic, intestinal, cardiac and bone marrow function, as well as physiological and physical status.

STUDY DESIGN:

A randomized double blind placebo controlled study over a 3-month period. Volunteers will be screened at Visit 1 and eligible subjects will, at visit 2, be randomized to either Sutherlandia frutescens (subsp. Microphylla) 1 x 400 mg capsules b.i.d or a placebo capsule of similar appearance. Visits 3, 4 and 5 (final) will be scheduled at monthly intervals. Safety tests will be repeated at each of the study visits (except visit 2). Patients will enter adverse events and daily use of study medication in a subject diary. This will serve as a measure of compliance.

SUBJECTS:

Inclusion criteria Healthy males and females between 18 and 45 years of age will:

be informed of the nature of the study and will give written informed consent,

have body weights within 25% of the appropriate weight range,

have no significant diseases or clinically significant abnormal laboratory values during screening,

have 12 lead ECG without significant abnormalities,

be on no regular medical treatment,

be able to communicate effectively with study personnel Exclusion criteria

Any disease or condition which might compromise the haematopoietic, renal, endocrine, pulmonary, central nervous, cardiovascular, immunological, dermatological, gastrointestinal or any other body system.




History of allergic conditions asthma, urticaria, eczema.

History of autoimmune disorders lupus erythematosis (SLE)

History or presence of dyspepsia, gastric ulcer or duodenal ulcer.

History of psychiatric disorders.

Intake of any medication within 14 days before start of the study

Recent history of alcoholism (

protocol understanding_ clinical data management_katalysthls

Health & Medicine