INTRODUCTION TO GOOD CLINICAL PRACTICE GCP IN RESEARCH

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INTRODUCTION TO GOOD CLINICAL PRACTICE (GCP) IN
RESEARCH

• DR. GODFREY BIEMBA
• MBCHB, DTMH, DLSHTM, MSC.
• EXECUTIVE DIRECTOR, CHAZ

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Workshop Objectives

• Understand Basic Concepts of Research
• Understand the Research Logic
• Appreciate the steps in a research proposal
• Understand Basics of Clinical trials
• Understand the concept of Good Clinical Practice
• Understand Basic Principles of Research Ethics
• Appreciate the practical challenges of conducting
  a clinical trial
• Understand the Current Projects
• Explore and Analyze the possible challenges of
  current research projects and devise an action
  plan to address them

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Introduction to Basic Concepts in Research 1 The
Research logic and basic steps in the research
process
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What is Research?

• Research refers to a search for an answer(s)
• This means there should first be a clear and
  valid question(s) to be answered The Research
  Question
• It means there should be a problem that has no
  clear solutions
• Once a problem has been identified, there should
  be a way of finding answers. This is generally
  referred to as Research Methodology.

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SELECTION OF APROBLEM REQUIRING RESEARCH

• Not every problem requires research
• Whether a problem requires research depends on
  three conditions
• i. There should be a perceived difference or
  discrepancy between what exists and the ideal or
  planned situation
• ii. The reason(s) for this difference should be
  unclear (so that it makes sense to develop a
  research question)
• iii. There should be more than one possible
  answer to the question or solution to the problem.

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The Research logic and basic steps in the
research process

• Identification of the problem,
• Identification of what has been done by other
  researchers to address the problem,
• Identification of an existing research gap
• Study Justification why carry out the study?
• What do we hope to achieve (Objectives)?
• What information/data do we need to collect in
  order to answer the question (s) or to address
  the problem?
• How do we collect that information?

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The Research logic and basic steps in the
research process

• How do we manage that information in order to get
  valid answers to our questions/problems? How do
  we know we have the answers?
• What are the threats to getting valid answers to
  our questions using the chosen research design
  and methods?
• Who will do what and when?
• What shall we need to do the study?
• How much will it cost?
• Who should know the results? How shall we let
  them know?

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The Research Logic
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The Research Logic
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The Research Logic
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The Research Proposal

• A scientific document that describes the
  hypothesis, aims, objectives, and methods of a
  proposed research project.
• For Clinical studies, this includes the protocol,
  which is a detailed plan of all that will be done
  from the enrollment of the study clients to the
  completion of the trial.

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Basic Stages of developing a Research Proposal

• Problem identification
• Problem Analysis
• Literature review
• Definition of Variables
• Objective setting
• Determination of the research design
• Definition of data collection tools
• Plan for data analysis
• Plan for publication and dissemination of
  research findings

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Characteristics of a Good Research Proposal

• Clear Statement of the Problem
• Well planned with clear objectives
• Builds on existing data, using positive and
  negative findings
• New data is intended to be utilized to answer
  original research question.

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Research Proposal format

• Take different forms dependent on donors,
  University, IRBs/IECs requirements
• Generally contain
• - The Title of the Project.
• - Introduction. This normally includes the
  background to the problem being addressed by the
  project, and the rationale for conducting the
  research.
• - Goals and Objectives Main aim of the
  project, hypothesis, and specific objectives.  

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Research Proposal format

• Study Design and Methods or Procedures Study
  design, the study population, the sample size,
  sampling methods, and the procedures.
•  Plan for Data Analysis. It is important that
  from the proposal stage the researcher indicates
  how they intend to analyze their data.
•  Ethical Consideration. 
• Work Plan  Budget.
• The Research Team. 
• References

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Introduction to Basic Concepts in Research 2
GCP, GMP, GLP, SOPs, Data Safety Monitoring Board.

• Hypothesis
• Null Hypothesis
• Good Clinical Practice (GCP)
• Good Manufacturing Practice (GMP)
• Good Laboratory Practice (GLP)
• Standard Operating Procedures (SOPs)
• Data Safety Monitoring Board (DSMB)
• Blinding
• Placebo
• Confounding

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Hypothesis

• What is a Hypothesis?
• A hypothesis is an "educated guess". It can be an
  educated guess about what nature is going to do,
  or about why nature does what it does.
• What makes a statement a scientific hypothesis,
  rather than just an interesting speculation? A
  scientific hypothesis must meet 2 requirements
• It must be testable
• It must be falsifiable
• Must be testable
• Science proceeds by making observations of nature
  (experiments). If a hypothesis does not generate
  any observational tests, there is nothing that a
  scientist can do with it. Arguing back-and-forth
  about what should happen, or what ought to
  happen, is not the way science makes progress.

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Hypothesis

• Consider this hypothesis
• Hypothesis A
• "Our universe is surrounded by another, larger
  universe, with which we can have absolutely no
  contact."
• This statement may or may not be true, but it is
  not a scientific hypothesis. By its very nature
  it is not testable. There are no observations
  that a scientist could make to tell whether or
  not the hypothesis is correct. Ideas such as
  Hypothesis A are interesting to think about, but
  science has nothing to say about them. Hypothesis
  A is a speculation, not a hypothesis.

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Hypothesis

• Hypothesis B
• "There are other inhabited planets in the
  universe."
• This hypothesis is testable, but it is not a
  scientific hypothesis. Here's why. Hypothesis B
  may be either correct or wrong. If it is correct,
  there are several ways that its correctness can
  be proven, including
• A space probe sent from earth to explore the
  universe sends back the news that it has
  discovered an inhabited planet. (This news is
  later confirmed by other space probes.)
• Radio telescopes on earth begin to receive
  signals from somewhere in the Andromeda Galaxy
  that appear to be reruns of the "I Love Telek"
  show.
• Knock, Knock. "Greetings, earthling! I am Telek
  from the planet Zoron in the Andromeda Galaxy. I
  have just landed in your backyard. Take me to
  your leader."

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Hypothesis

• So, if Hypothesis B is true, there are
  observations that scientists could make that
  would prove its correctness. But, the hypothesis
  may be wrong. (Most hypotheses are...) If
  Hypothesis B is wrong, there is no test that will
  prove it. If one of our space probes never finds
  an inhabited planet, it doesn't mean that one
  doesn't exist. If we never receive signals from
  space, or Telek never lands in your back yard,
  that does not prove that the hypothesis is wrong,
  either. Hypothesis B is not falsifiable.

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Hypothesis

• What about this
• Hypothesis C "Any two objects dropped from the
  same height above the surface of the earth will
  hit the ground at the same time, as long as air
  resistance is not a factor."
• Hypothesis C is a scientific hypothesis because
• It is testable - pick 2 objects, and drop them.
  Of course, you may have to provide a vacuum for
  them to fall in, in order to remove air
  resistance from consideration.
• It is falsifiable - If anyone finds 2 objects
  that don't hit the ground at the same time and
  can show that it is not due to air resistance,
  then she has proven the hypothesis wrong. This
  hypothesis "sticks its neck out" for every test.
  In theory and in practice, if Hypothesis C were
  wrong, it would be very easy and straightforward
  to show it.

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Null Hypothesis

• In statistics a null hypothesis is a hypothesis
  set up to be nullified or refuted in order to
  support an alternative hypothesis. When used, the
  null hypothesis is presumed true until
  statistical evidence in the form of a hypothesis
  test indicates otherwise. The use of the null
  hypothesis is controversial
• The null hypothesis is generally that which is
  presumed to be true initially. Hence, we reject
  only when we are quite sure that it is false,
  often 90, 95, or 99 confident that the data do
  not support it.

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GCP1 What is GCP?

• An international ethical and scientific quality
  standard for designing, conducting, recording,
  monitoring, auditing, analyzing, and reporting of
  clinical trials that involve the participation of
  human subjects.
• Compliance with this standard provides public
  assurance that the data and reported results are
  credible and accurate, and that the rights,
  safety and well-being of trial subjects are
  protected, consistent with the principles that
  have their origin in the Declaration of Helsinki.

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THE PRINCIPLES OF GCP

• Clinical trials should be conducted in accordance
  with the ethical principles and consistent with
  GCP.
• A trial should be conducted only if the benefits
  outweighs risks to both the subjects and society
• The rights, safety, and well-being of the trial
  subjects should prevail over interests of science
  and society.

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THE PRINCIPLES OF ICH GCP

• Clinical trials should be scientifically sound,
  and described in a clear, detailed protocol.
• A trial should be conducted in compliance with
  the protocol that has been approved by the
  IRB/IEC.
• The medical care given to, and medical decisions
  made on behalf of, subjects should always be the
  responsibility of a qualified physician or, when
  appropriate, of a qualified dentist.

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THE PRINCIPLES OF ICH GCP

• Each individual involved in conducting a trial
  should be qualified by education, training, and
  experience to perform his or her respective
  task(s).
• Freely given informed consent should be obtained
  from every subject prior to clinical trial
  participation.

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THE PRINCIPLES OF ICH GCP

• All clinical trial information should be
  recorded, handled, and stored in a way that
  allows its accurate reporting,interpretation and
  verification.
• The confidentiality of records that could
  identify subjects should be protected, respecting
  the privacy and confidentiality rules in
  accordance with the applicable regulatory
  requirement(s).

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THE PRINCIPLES OF ICH GCP

• Investigational products should be manufactured,
  handled, and stored in accordance with applicable
  good manufacturing practice (GMP). They should
• be used in accordance with the approved
  protocol.
• Systems with procedures that assure the quality
  of every aspect of the trial should be
  implemented.

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Good Laboratory Practice

• Good Laboratory Practice (GLP) embodies a set of
  principles that provides a framework within which
  laboratory studies are planned, performed,
  monitored, recorded, reported and archived. These
  studies are undertaken to generate data by which
  the hazards and risks to users, consumers and
  third parties, including the environment, can be
  assessed for pharmaceuticals, agrochemicals,
  cosmetics, food and feed additives and
  contaminants, novel foods and biocides. GLP helps
  assure regulatory authorities that the data
  submitted are a true reflection of the results
  obtained during the study and can therefore be
  relied upon when making risk/safety assessments. 

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Good Manufacturing Practice

• Good Manufacturing Practice means the part of the
  quality assurance which ensures that medicinal
  products are consistently produced and controlled
  to the quality standards appropriate to their
  intended use.
• Good Manufacturing Practice is an international
  set of guidelines by which drugs and medical
  devices are manufactured.
• A recommendation for "Good Manufacturing
  Practice", first issued in by the World Health
  Organization (WHO) in 1968, that ensures that the
  products are manufactured and tested invariably
  in compliance with the prescribed quality
  standards

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Standard Operating Procedures (SOPs)

• Detailed, written instructions to achieve
  uniformity of the performance of a specific
  function.

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GCP2 Designing, Conducting and Monitoring
Clinical Trials under GCP
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COHORT STUDT DESIGN
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Case Control Study
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THE CLINICAL TRIAL
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Clinical Trials

• Carefully designed scientific studies aimed at
  finding out the safety and efficacy of a
  particular drug or intervention.
• They answer the following questions regarding a
  drug or an intervention Is the drug safe? Does
  it work? Is it safe when used over a long period
  of time? Does it work in many people over a long
  period of time? Are there any long term side
  effects?

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PHASES OF A CLINICAL TRIAL

• PRE-CLINICAL STUDIES

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PRE-CLINICAL STUDIES

• In vitro testslaboratory experiments to find out
  if a new drug works on human cells in test tubes.
  
• Animal studies These are meant to ascertain
  efficacy and safety of the drug or intervention
  in living creatures.

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CLINICAL STUDIES

• Phase1 Safety trials.
• Phase 2 The dose that has been found to be safe
  in phase1 is given to a larger number of
  participants over a longer period of time to see
  if the drug really works and see if there are
  long term side-effects.

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CLINICAL STUDIES

• Phase 3 The trial drug is given to a much larger
  group of participants usually in many research
  centers (multi-center trials) over many months or
  even years to see if the drug remains useful or
  has any side effects that only show after long
  term use.
• Phase 4 Post-marketing trials. These trials
  could as well be called surveillance studies
  because they are meant to monitor side-effects or
  problems that may show up after several years of
  use.

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Types of Clinical trials.

• Randomized controlled trial divides participants
  randomly into two test groups using computer
  generated random numbers
• Double-blind controlled trialensures that
  neither the participants nor the researchers know
  who has received which treatment
• Randomized double-blind controlled studywhich
  combines both control measures.
• Randomized open label placebo controlled
  cross-over trial

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Conducting Clinical Trials

• Screening
• Enrollment
• Patient management and Monitoring
• Data management/recording
• Discharge
• Follow-up

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Screening

• Inclusion and Exclusion Criteria

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Enrollment Procedure

• Assess for admission to study (See Inclusion
  Criteria).
• Do a general physical exam including
  Temperature, Pulse, BCS, assess Pallor, Jaundice,
  Petechiae.
• Do lab investigations
• Get Informed Consent from Parent or Guardian if
  patient qualifies for study.
• Enroll the patient and give study Identification
  Number (SIN)
• Do all Admission Routine as per Flow-sheet or
  CRF.

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Revision Slide GCP

• A Quality and Ethical Standard that guides the
  conduct of Clinical Trials from the design stage
  to the Publication of results.

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Laboratory Procedures

• The Procedures
• Timing
• Quality control
• Communication with Clinical staff
• Storage of specimens for transportation
• Labeling Name, Age, Sex, Date, Time, Study No.

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Discharge Procedure

• Do all discharge orders as per flow-sheet
• Make sure you have all your contact persons full
  name and residential address
• Inform the parent or guardian who they should see
  on review, when and where.
• Give name of all alternative persons for the
  parent/guardian to see if at time of review a
  specific officer is not there,
• Deal with all possible transport issues
  necessary,
• Find out if the address given is permanent or
  they are just visiting.

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Follow up Procedure

• Ensure that the flow-sheet has all necessary
  information for follow-up including landmarks to
  find the village
• Have a direction map on the discharge/follow up
  form
• Field officer to be there at discharge time to
  appraise himself with the directions and names of
  contact persons
• Have good register of all discharged patients
• Liase well with Clinical monitors
• Create a computer data base with a prop-up
  facility to remind you of due and
  overdue(24hours) follow-ups.
• All defaulting patients must be followed up
  promptly.

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Data and Safety Monitoring

• Includes Clinical care of the patient
• Ensures the safety and wellbeing of the patient
• Data Safety Monitoring Board
• The Flow-sheet Follow the flow-sheet

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Data Safety Monitoring Board

• A group of independent researchers who review the
  data while a clinical trial is going on, to
  determine if one drug is markedly safer or more
  effective than another.
• Oversees and monitors clinical trials to ensure
  participant safety and data validity and
  integrity.

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Data Management

• Data Collection-tools, e.g. Flow-sheets, CRFs
• Data entry and storage-data bases, spreadsheets
  and manual storage (filing).
• Data Analysis-data must be entered on data bases
  or spreadsheets in analysable form
• - Different computer packages for data analysis,
  e.g. Systat/Stata/Epi-info/SPSS
• Publication and dissemination- Abstracts,
  Publication into peer reviewed Scientific
  Journals.

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Introduction to Data Processing and Data Analysis
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Data Processing and Analysis

• Data Processing
• Collection
• Recording
• Data entry/Data security
• Quality controls(including plan for handling of
  missing data)Data cleaning, checking for
  completeness and internal consistency
• Analysis

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Planning for Data Analysis

• You MUST PLAN for Data Analysis at the DESIGN
  STAGE
• To ensure collection of NECESSARY Data
• To reduce collection of UN-NECESSARY Data
• Aim to Answer the main research question link
  your analysis to your main and specific objectives

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Basic Steps in Quantitative Data Analysis

• 1.0 Clean your data
• Check for errors
• 2.0 Basic Descriptive analyses
• basic description of the data.
• summary statisticsFrequency tables, Proportions,
  Mean, Range, Mode, etc.
• graphical presentations
• Bar charts, Histograms, etc.

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Basic Steps in Data Analysis

• 3.0 Analyse Associations
• Crude Univariate analyses
• Classical methods are used for univariate
  analysis to give an initial idea of the
  relationship between the outcome and explanatory
  variables within the dataset.
• Estimate the magnitude of the difference in
  outcome between exposure groupsestimate risk
  ratio
• Determine if the observed difference could be
  explained by Chance(Significance testing)

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Is the observed difference true or just due to
chance?

• Start with the Null hypothesis that theres no
  difference between the groups
• Test the Null hypothesis with an appropriate
  test Chi, Z-test, Fischers exact test(t-test),
  etc.

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INTRODUCTION TO RESEARCH ETHICS

• -DR. GODFREY BIEMBA-
• MBCHB, DTMH, DLSHTM, M.SC Executive Director,
  CHAZ, Chair-NHRAC, member UNZA REC

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AIMS OF THE SESSION

• Understand Basic Principles of Ethics
• Understand the importance of protecting the
  rights of study subjects by means of the process
  of informed consent
• Understand how to complete the forms for
  submission to Research Ethics Committee

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RESEARCH ETHICS

• What is Ethics?
• Morality
• Right or Wrong
• What is Morality?
• Right (good) and wrong (bad) in human actions,
  conduct and behaviour.
• What is Ethos?
• a professional code of conduct relevant to a
  particular occupation
• Ethical code or standard

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RESEARCH ETHICS

• Ethics and morality may be descriptive by
  observing the way human beings behave or
  normative by trying to figure out the right
  course of action to take in a particular
  circumstance.
• Abuses in health research in the past led to the
  development of the current international ethical
  guidelines in biomedical research.
• Example Tuskegee Syphilis Study (1932-1972)
  Poor African American men were deceived and
  observed for untreated syphilis.

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International Ethical Guidelines

• Declaration of Helsinki (1964/1975/1983/1989/1996/
  2000, on biomedical research involving human
  subjects)
• International Ethical Guidelines for Biomedical
  Research Involving Human Subjects (CIOMS
  WHO1993)
• World Health Organization Good Clinical Practice
  Guideline (WHO GCP 1995)
• International Conference on Harmonization Good
  Clinical Practice Guideline (ICH GCP 1996)
• Ethics Considerations in HIV Preventive Vaccine
  Research (UNAIDS 2000).

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FUNDAMENTAL CONSIDERATIONS IN RESEARCH

• Scientific design,
• Care of the research participants,
• Ethics and scientific standards,
• The communities in which the research takes
  place.

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Principles of Biomedical Ethics

• Autonomy
• Individuals should be treated as autonomous
  agents.
• Participation in a research project should be
  voluntary and with adequate information no undue
  coercion.
• Beneficence/Non-Maleficence
• Do not harm
• Maximize possible benefits and minimize
  possible harm.
• Justice An injustice occurs when some benefit to
  which a person is entitled is denied without good
  reason or when some burden is imposed unduly.

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Ethical Guidelines

• Physicians duty to protect the life, health,
  privacy, and dignity of the human subject.
• Medical research involving human subjects must
  conform to generally accepted scientific ethical
  principles.
• The research protocol should always contain a
  statement of the ethical considerations involved
  and should indicate that there is compliance with
  international ethical guidelines.
• The subjects must be volunteers and informed
  participants in the research project.

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What makes Clinical Research Ethical?

• Social or Scientific Value
• Scientific Validity
• Fair Subject Selection
• Favourable risk-benefit ratio
• Independent review
• Informed Consent
• Respect for potential and enrolled subjects

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UNZA ETHICAL GUIDELNES

• Submit proposal to Secretary of Research and
  Ethics Committee
• Submission should include
• - 20 copies of application form,
• 4 copies of full protocol,
• Any questionnaires in four copies
• Informed consent in four copies
• 4 copies of Principal Investigators CV
• 4 copies of approval from appropriate research
  committee or Research Technical Committee
• 4 copies of External Ethical Approval Letter

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The Informed Consent Process

• Dr. Godfrey Biemba
• MBCHB, DTMH, DLSHTM, MSC
• Executive Director, CHAZ

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Informed Consent

• Respect for persons requires that subjects, to
  the degree that they are capable, be given the
  opportunity to choose what shall or shall not
  happen to them.
• Consent Form must contain at least three
  elements
• a) Information
• b) Understanding/Comprehension
• c) Voluntariness

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Informed ConsentInformation

• - This means full disclosure of information,
  unless such disclosure impairs the validity of
  the research. This is only justified if, there
  are no undisclosed risks that are more than
  minimum and there are plans to debrief the
  subjects when appropriate.
• - Includes that it is a research project, the
  procedures, risks, benefits, alternative
  procedures, a statement offering the subject the
  opportunity to ask questions(including name and
  address of the person to ask questions) and to
  withdraw at any time from the research without
  compromising present or future care.

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Informed Consent

• Comprehension - The manner and context in which
  information is presented is as important as the
  information itself.
• - Avoid technical jargon, use local language
  translation
• Voluntariness - Requires conditions free of
  coercion and undue influence.

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The Informed Consent Process

• It is a Process, not a one time event
• Involves four stages
• Verbal Discussion - Doctor has preliminary
  discussions with patient to explain diagnosis,
  prognosis and treatment options, both standard
  and investigational.
• Information sheet and Consent Forms - The patient
  is given (explained) an information sheet which
  contains comprehensive details of study treatment
  including rationale for study, possible benefits
  as well as adverse effects sub-divided into
  likely, less likely and remote possibilities.
• Discussion - The trial is again explained to the
  patient and the patient encouraged to ask
  questions.
• On going dialogue The Doctor and
  patient/guardian engage in an ongoing dialogue
• Based on four basic principles Do good, Do No
  Harm, Autonomy, Justice.

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The Informed Consent Process-Adequate disclosure
and maintenance of Consent-

• What constitutes adequate disclosure of
  information? How much information is considered
  "adequate"?
• reasonable physician standard what would a
  typical physician say about this intervention?
• reasonable patient standard what would the
  average patient need to know in order to be an
  informed participant in the decision?
• subjective standard 1 what would this patient
  need to know and understand in order to make an
  informed decision?
• subjective standard 2what would this patient and
  relatives need to know and understand in order to
  maintain their informed decision?

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The Informed Consent Process-Maintaining the
Informed Consent-

• Barriers to refusal and maintenance of consent
• Communication barriers
• Misperceptions
• Misconceptions
• Concerns over the protocol and the implications
• Poor motivation

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The Informed Consent Process-Maintaining the
Informed Consent-

• Communication Develop a communication strategy
  (Mapping strategy)
• Identify main issues at each stage of the
  research
• Develop appropriate messages to address the
  issues
• Develop strategies/ways of communication to
  address the issues
• Maintain effective communication
• Motivation
• Identify motivating and de-motivating factors
• Address de-motivating factors
• Put in place motivators
• Misconceptions and Misperceptions
• These arise from ineffective communication
• They also arise from inherent cultural beliefs a
  thorough understanding of these beliefs is part
  of the answer to addressing them.
• Effective Counseling is vital in addressing
  these this requires full and continuous DIALOGUE

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Compliance with GCP

• Is the design scientifically and ethically sound?
• Is the Study Protocol Clinically, ethically and
  scientifically sound?
• Is there an Informed Consent Process following
  international ethical standards?
• Is there an efficacy and safety monitoring system
  in place
• Is there a quality assurance system in place at
  all levels of the study process (screening,
  enrollment, data collection/recording, patient
  monitoring, data entry)?
• Is there evidence that the trial drug has been
  produced under GMP?

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Current Project COARTEM STUDY

• Study Purpose To obtain efficacy, safety,
  tolerability and pharmacokinetic data of Coartem
  dispersible tablet formulation for oral
  suspension in infants and children equal or less
  than 12 years with body weight/gt5kg and lt35kg
  suffering from acute uncomplicated P. falciparum
  malaria in order to gain regulatory approval for
  to make Coartem paediatric formulation available
  for clinical use in Africa.

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Current Project COARTEM STUDY

• Primary Objective
• To confirm the efficacy of Coartem paediatric
  formulationby testing the hypothesis that
  Coartem 6-dose regimen paediatric formulation is
  non-inferior to the presently used Coartem 6-dose
  regimen of crushed conventional tablet
  formulation on the 28-day Polymerase Chain
  Reaction (PCR)-corrected parasitological cure
  rate.

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Current Project COARTEM STUDY

• Secondary Objectives
• To compare 7-day parasitological cure rate, 14
  day PCR correlated parasitological cure rates
  between the two treatment groups
• To compare time to parasite, fever, and
  gametocyte clearance between the two treatment
  groups
• To compare the safety and tolerability profile of
  the two treament groups on Adverse Events,
  general laboratory, vital signs and ECG
  measurements
• Exploratory Objectives
• To explore the incidence of early treatment
  failures with the paediatric formulation

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Current Project COARTEM STUDY

• Design Randomized, investigator-blinded,
  multicentre, parallel group study to compare
  efficacy, safety and tolerability of Coartem
  dispersible tablet formulation vs. Coartem 6 dose
  crushed tablet in the treatment of acute
  uncomplicated P. Falciparum malaria in infants
  and children.
• Group1 /gt5kg - lt15kg
• Group2 15kg - lt25kg
• Group3 25 kg - lt35kg

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COARTEM STUDY Study Size and Interim Analysis

• Initially 160 patients will be enrolled
• Interim Analysis will be performed by DSMB for
  perceived futility for efficacy as the new
  formulation has never been tested in humans
• No more patients to be enrolled till completion
  of interim analysis and recommendation by DSMB to
  continue or otherwise

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Protection of Human Subjects,Data and Safety
Monitoring

• Informed Consent will be obtained
• Serious Adverse Events (SAEs) experienced within
  4-weeks of study must be reported to Norvatis
  within 24hours or occurrence
• Site Monitoring
• Data management and Quality Control system in
  place
• Data from CRFs entered on databse by expert
  research organization using a proven SOPs
• Entered data checked for errors by data
  management staff
• DSMB in place

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Does the Coartem Study Comply with GCP?

• Is the design scientifically and ethically sound?
• Is the Study Protocol Clinically, ethically and
  scientifically sound?
• Is there an Informed Consent Process following
  international ethical standards?
• Is there an efficacy and safety monitoring system
  in place
• Is there a quality assurance system in place at
  all levels of the study process (screening,
  enrollment, data collection/recording, patient
  monitoring, data entry)?
• Is there evidence that the trial drug has been
  produced under GMP?