Saturday, 8 October 2011

NOTES FOR PROTOCOL




Subject
Sponsor
Investigator
Statisticians
Clinical Development Associates
Clinical Research Associates
Scientific Communications
Data Collection Coordinators
Data capture
Data Analysts
Load Analysts
Decision Support Analysts
Study Drug coordinators
FDA



PHARMA PROCESS

Need for a drug
Discovery of a molecule through research
Drug development through clinical trails
Regulatory approval
Manufacturing the drug in large scale
Marketing of drug

What happens during a clinical trail?
Trail Team
 Doctors
 Nurses
 Social workers
 Health care professionals
              
·       Check health of participant at beginning of trail
·       Give specific instructions for participating in trail
·       Monitor participant carefully during trail
·       Stay in touch after trail is completed

Investigational New Drug (I N D)
                            
IND application submitted to CDER
Application consists of
Results of animal studies
Proposed plans for study in humans

Clinical trail

Study of an investigational product in human subjects
Intended to discover or verify
Clinical effect (safety/efficacy)
Pharmacokinetic effect (ADME)
Adverse reactions

Side effects & Adverse reactions 
Side effects are any undesired actions or effects of drug or treatment
Negative or adverse effects may include headache, nausea,
hair loss, skin irritation, or other physical problems

Toxicity: An adverse effect produced by a drug  that is

Detrimental to the participants health . The level of toxicity

associated with a drug will vary depending on the condition

which the drug is used to treat.


Various Steps in Clinical Trail

Plan and Design Study
Conduct the study
Study wrap up



Plan /Design (study development process)

Prepare  study design for data collection
Deliver protocol/CRF &SAP
Business partners meet, discuss & decide
Flexible process

Protocol (sample)
Set of instructions how to study will be conducted
Deliverable to FDA
One per clinical trail (study or treatment)
Study drug/Study design, blinding, Randomization details
Inclusion/exclusion criteria
Informed consent
Lab details
Efficay, Pharmacokinetic and safety Evaluation
AE motoring / reporting
Informed consent
Doctors & Nurses involved in trail explain details of study to participant
Learning key facts about a clinical trail before deciding whether
Or not to participate
Continuous process through out study to provide information
for participant
Treatment
Treatment Administered
Materials & supplies
Method of Assignment to treatment
Rational for selection of Doses in the study
Selection and timing of doses
Blinding
Concomitant Therapy
Treatment compliance
Efficacy, Pharmacokinetic and safety Evaluation
Efficacy measures
1.    Primary Efficacy measures
2.    secondary Efficacy measures
3.    Efficacy Criteria
Drug Concentration measurements (pharmacokinetic
Assessment)
Safety Evaluation
Study Wrap-up
Preparation of clinical study report (CSR)
Additional integrated analysis & submit to FDA or
Regulatory authority for approval
Randomization  
Randomization is a process by which each participant has same chance of being assigned to either intervention (study drug) or control (placebo)
Benefits
·       Removes potential investigator bias in allocation of participant to intervention and control
·       Creates comparable groups to either intervention or control
·       Validity of statistical test guaranteed
Because of bias non-randomized study may show better result
Compared to randomized which is reality is not true
Randomization facilitates efficient drugs success
NO of studies/patients       Study design         Results
8/3000 patients                  Non-randomized   5/8 good result
6/3000patietns                   Randomized           1/6good result

Benefits  :    A method based on chance by which study
Participants are assigned to treatment group.                     
Randomization minimizes the differences among groups
by equally distributing people with particular characteristics
among all the trail arms. The researchers do not know which
treatment is better. From what is known at the time any one of
the treatments chosen could be of benefit to the participant.
Randomized Trail: A study in which participants are
randomized assigned to one of two more treatment arms
of a clinical trail. Occasionally placebos are utilized.

ARM:     Any of the treatment groups in a randomized trail.
                Most randomized trails have two “Arms” but some
                have three “Arms” or even more
 
Blind (Masked) :
A randomized trail is “Blind” if the participant is not told which arm of the trail he is on
Patient /Investigator/statisticians or all, not aware of medication
being given
Study drug or placebo or comp drug
Subject Binding – Eliminates psychological bias
Statisticians Blinding – Eliminates analysis bias
Single Blinded: Only patient not aware
Double blinded: Patient and Investigator – not aware
(Statisticians also not aware)
Un blinded study is called open label study
                                 
Blinding /Randomization
             Blinded                         Randomization
              Yes                                  Yes
              Yes                                  No
              No                                   Yes
              No                                   No


Baseline:
1) Information gathered at the beginning of a study from
   which   variations found in the study are measured .
2) A known value or quantity with which an unknown
    is compared when measured or assessed.
3) The initial time point in a clinical trail, just before a 
    Participant starts to receive the experimental treatment
   Which is being tested.At this reference point,measurable
   Values such as vitals are recorded

Placebo
Inactive pill, liquid, or powder that has no treatment value
Experimental treatments are often compared with placebos
Patients in control group will receive a placebo or
Standard drug instead of an active drug or treatment
Patients in Intervention group or Study group will receive
Active drug or study drug or investigational drug

Case Report form
Forms used to capture information about patient participating
in clinical trail
About 60 to 100 forms will packaged visit wise
Each CRF will be IT module with edits
PHARMACOKINETICS :
The Process (in a living organism) of absorption, distribution,
metabolism, and excretion of a drug or vaccine

PEER REVIEW: Review of a clinical trails by experts chosen
by the study sponsor, These experts review the trails for
scientific merit, participant safety, and ethical considerations  

DSMB:    Data safety and monitoring board, An independent
Committee of community representatives and clinical research
experts ,that reviews data while a clinical trail is in progress
to ensure that participants are not exposed to undue risk
A DSMB may recommend that a trail be stopped if there are
Safety concerns of if the trail objectives have been achieved.

Institutional Review  Board (IRB) :
A committee of physicians, statisticians ,researchers,community
Advocates,and others that ensures that a clinical trail is ethical
And that the rights of study participants are protected.
All clinical trails in the U.S must be approved by an IRB before
Begin
Every institution that conducts or supports biomedical
Or behavioral research involving human participants must,
By federal regulation, have an IRB that initially approves and
Periodically reviews the research in order to protect rights of
human participants.
Statistical Plan
Advance plan for stats to analyze the clinical data
Shred with FDA
Steps in Study development
1)   Questions /concepts
2)   Model report Concepts
3)   Output concepts
4)   Data collection concepts
5)   Draft output
6)   Draft data collection
7)   Draft protocol
8)   IT Module review
9)   CRF completion
10)                Data validation planning

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