CLINICAL TRAIL by thilak0505


            Presented by:


St. Peter’s Institute of Pharmaceutical
      Vidyanagar, Hanamkonda.
     Why Do we conduct Research

• To collect data on usual and unusual
  events, conditions, & population
• To test hypotheses formulated from
• To understand better one’s
Classifications of Research Studies

Three main types are there

Observational Studies:
• Groups are studied & contrasts made
  between groups
• The observed data collected are analyzed
Analytic Studies:
Also called Experimental
 Study the impact of a certain therapy
 Ultimately the investigator controls factor being

Clinical Trial:
Considered the “true” experimental study
“Gold Standard” of clinical research
Often a prospective study that compares the effect
  and value of an intervention against a control in
  human subjects
 The Different Study Designs
• Case-control    • Cohort
• Case Reports    • Case Series
• Outcomes Based: • Survey Research:
     Quality of Life     Questionnaires
     Decision analysis          Polls
     Economic Analysis          Surveys
• Meta Analyses
• Survival Analysis
• Randomized Clinical Trial
• Cross-sectional Study: Presence or absence
  of exposure to possible risk factor measured at
  one point in time. Prevalence obtained.
• Prevalence: The # of new cases and existing
  cases during specified time period.
• Incidence: The # of NEW cases per unit of a
  population at risk for disease occurring during
  stated time period.
    Historical Highlights of Drug
• 1909: Paul Ehrlich - Arsphenamine
• 1929: Alexander Fleming - Penicillin
• 1935: Gerhard Domagk - Sulfonamide
• 1944: Schatz/Bugie/Waksman –
• By 1950, the British Medical Res.
  Council developed a systematic
  methodology for studying & evaluating
  therapeutic interventions
Components of Clinical Trials
• Involve human subjects
• Move forward in time
• Most have a comparison CONTROL group
• Must have method to measure intervention
• Focus on unknowns: effect of medication
• Must be done before medication is part of
  standard of care
• Conducted early in the development of
     Clinical Trial Designs
• Randomized/blinded trial
• Randomized/double blinded trial
• Non-randomized concurrent controlled
• Placebo trial
• Historical controlled trial
• Crossover Trial
• Withdrawal trial

• Randomized:             Blinded: Participants
  Schemes used to           do not know if in
  assign participant to     experimental or
  one group                 control group
  o   Ex: Every 3 gets
      higher dose         Double Blinded:
• Nonrandomized: All        Participants AND
  with Hep. C = cases;      staff do not know
  others = controls         group assignment
• Protocol: Study         Placebo: Inactive pill
  design - instructions     with no therapeutic
       Components of Clinical Trial
• Investigating two or more conditions so
  have two(+) groups
    • Ex: drug vs. placebo; medicine vs.
      surgery; low dose vs. high dose
•   Specific inclusion/exclusion criteria
•   Sample size & power calculations
•   Plan re: potential biases
•   Plan re: handling of attrition/loss to
    follow up
Study Participant Recruitment
• Identify eligible
• Explain study
• Provide informed
• Reassess
• Assign to one
Participants should be told:
• May have side effects (adverse effects)
• Time commitment
• Benefits & risks
• May withdraw at any time
• Enrollment 100% voluntary
    Phases of Clinical Trials
• Most trials that involve new drugs go
  through a series of steps:
   – #1: Experiments in the laboratory
   – #2: Once deemed safe, go through 1-
     4 phases
    Phases of Clinical Trials
• Phase I: Small group [20-80] for 1st time
  to evaluate safety, determine safe dosage
  range & identify SE

• Phase II: Rx/tx given to larger group [100-
  300] to confirm effectiveness, monitor SE,
  & further evaluate safety
     Phases of Clinical Trials
• Phase III: Rx/tx given to even larger group
  [1,000-3,000] to fulfill all of Phase II objectives &
  compare it to other commonly used txs & collect
  data that will allow it to be used safely

• Phase IV: Done after rx/tx has been marketed -
  studies continue to test rx/tx to collect data about
  effects in various populations & SE from long
  term use.
    Clinical trails at a glance.
        #         Length Purpose          % Drugs
        Subs.                             Tested

Phase   20 – 100 Several     Mainly Safety 70%
I                months

Phase   Up to     Several Short term     33%
II      several   months- safety; mainly
        100       2 yrs.  effectiveness
Phase   100s –    1-4 yrs.   Safety,       25-30%
III     several              dosage &
        1000                 effectiveness
      Ethics of Clinical Trials:
      Protection of Participants
3 ethical principles guide clinical
• Respect for Persons: Treatment of person
  as autonomous
• Beneficence: Issue re: potential conflict
  between good of society vs. individual
• Justice: Treatment of all fairly & all equally
  share benefits & risks
Ethical Norms of Clinical Trials

Sound study designs take into account:
• Randomization or sharing of risks
• Proper use of placebo
• Processes to monitor safety of rx/tx
• Competent investigators
• Informed consent
• Equitable selection of participants
• Compensation for study related injuries
       Ethical Issues: Protection of
             Human Subjects
• Rely on integrity of Investigator but outside groups
  also have oversight
• Participants’ rights protected by Institutional Review
  Boards [IRBs]

   o   An IRB is defined as: "any board, committee or
       other group formally designated by an institution
       to review, to approve the initiation of, and to
       conduct periodic review of biomedical research
       involving human subjects"
 Human Subjects’ Protection
IRB responsible for such tasks:
• Review research to ensure that potential
  benefits outweigh risks
• Develop and issue written procedures
• Review research for risk/benefit analysis &
  proper protection of subjects
• Issue written notice of approval/disapproval to
  the Investigator
• Review and respond to proposed protocol
  changes submitted by the Investigator
    IRB Responsibilities (continued):

• Review reports of deaths, and serious and
  unexpected adverse events received from
  the Investigator
• Conduct periodic continuing review of the
  study, study risks, selection of subjects,
  privacy of subjects, confidentiality of data,
  and the consent process
    10 Key Points to be Noted
• Voluntary informed consent
• Experiment must be for the good of society, & results not
  obtainable by other means
• Experiment should be based upon prior animal studies
• Physical & mental suffering & injury should be avoided
• No expectation that death/disabling injury will occur from the
• Risk vs. benefit
• Protect subjects against injury, disability, or death
• Only scientifically qualified persons to be involved
• Subject can terminate her/his involvement
          Informed Consent:
 A Part of Human Subject Protection
            Objectives of Informed Consent
To Ensure:
     • Voluntariness
     • Comprehension
     • Information
To Demonstrate That:
     • Person freely gave consent to participate
     • Consent given by a competent person
     • Person has been given all information
     • Person knows this is research – not treatment
     Components of Informed
 Must Include the Following Information:
• Why research being done?
• What researchers want to accomplish
• What will be done and for how long
• Risks & benefits of trial
• Other treatments available
• Can withdraw from trial whenever desire
• Compensation for unexpected injuries
     Vulnerable Populations
Groups thought not to have autonomy to give informed
   • children
   • mentally impaired, individuals with dementia
   • Prisoners
Who may be unduly influenced to participate:
   • students
   • subordinates
   • pregnant women (actually, the fetuses)
   • patients (care-giver vs. researcher)
   Inclusion in Clinical Trials
• Historically women were excluded if of
  reproductive age (ages 18-45)
• Fear of harm to potential unborn child
• In essence, excluded MAJORITY of
• New guidelines eliminates this stipulation
Participation in Clinical Trials
Why Some                  Why Some Do Not?
  Participate:            • Mistrust of studies
Give back to society      • Do not want to be
Exhausted all other txs     “guinea pig”
Health care services      • Do not meet criteria
Payment & incentives      • Cannot give up time for
Support                     study visits
Others??                  • Barriers: lang.,
    Taking Part in Research Studies:
           Questions to Ask

• What is study about?
• What are the goals?
• Study sponsor?
• Participant input into
• Inclusion criteria?
• Benefits & risks
• Is there an incentive?
• How protected from harm?
• What is required: # study visit & what
• What happens after study is over?
• How results will be disseminated?
        The Impact of Studies
• Some clinical trials have been critical to
  patient health & provision of health care
• For instance:
  o   Protocol 076:  HIV perinatal transmission
  o   1st trial of AZT
  o   Various cancer treatments
  o   Development of other HIV related medications
      like PIs
        The Impact of Studies
Other clinical trials have not been as
successful for a variety of reasons:

•   Medications did not work as in laboratory
•   Loss to Follow-Up of too many patients
•   Harmful substance
•   Unethical & poorly conducted study (Ex:
    Tuskegee Study & recent Gene Replacement
• Clinical trails are a valuable part in drug
  discovery & development.
• Huge costs are involved in conducting
  clinical trails, so a careful planning is
  necessary to avoid mistakes and risk
  involved with clinical trails.
• And a succesful trail leads to launch of
  new drug to people & profits to company.

• Understanding Clinical Trials Developed by Sara
  Back, NP Bronx-Lebanon Hospital Center.

• The Process of New Drug Discovery and
  Development Edited by Charles G. Smith Ph.D.
  James T. O’Donnell Pharm.D. Second Edition

• National Institute of Dental and Craniofacial

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