complete description of document required for clinical trial

1. By:
Ankit SharmA
M.Pharma 2nd sem
Pharmacology
Bhupal Noble University,Udaipur

2. Clinical Trials : Introduction
 The International Conference on Harmonization defines a
clinical trials as, Any investigation in humans subjects
intended to discover or verify the clinical, pharmacological
and/or other pharmacodynamic effects of an investigational
product, and/or to identify any ADR to an investigational
drugs, and/or to study ADME of drug with the objective of
ascertaining the safety and efficacy .
 This is also termed as randomized control trial .
 Clinical trials are a set of procedures in medical
research conducted to allow safety and efficacy data to be
collected for health interventions.
Bhupal Noble University,Udaipur

3. Different Types of
Clinical Trials
Treatment trials - test new treatment, new combinations of drugs,
or new approaches to surgery or radiation therapy (for people with a
particular disease).
Prevention trials - look for better ways to prevent disease in people
who have never had the disease or to prevent a disease from
returning. These approaches may include medicines, vitamins,
vaccines, minerals or lifestyle changes.
Screening trials – test the best way to detect certain diseases or
health conditions.
Quality of life trials ( or supportive care trials) – explore ways to
improve comfort and the quality of life for individuals with a chronic
illness
Bhupal Noble University,Udaipur

4. Different Phases of
Clinical Trials
Clinical trials are conducted in phases. The trials at each phase have a different
purpose and help scientists answer different questions:
 In Phase I trials, researchers test a new drug or treatment in a small group of
healthy people ( 20 -50) for the first time to evaluate its safety, determine a safe
dosage range.
 In Phase II trials, the study drug or treatment is given to a selected group of
patients (100 – 300) to see if it is effective and to further evaluate its safety.
 In Phase III trials, the study drug or treatment is given to a large group of patients
( 1000 – 3000) to confirm its effectiveness, monitor side effects, compare it to
commonly used treatments, and collect information that will allow the drug or
treatment to be used safely.
 In Phase IV trials, post marketing studies delineate additional information
including the drug’s risks, benefits and optimal use.Bhupal Noble University,Udaipur

5. The Clinical Trial Application
 Covering letter
 Completed Application form (CTF1)
 Cover sheet
 Checklist
 Final version of the Clinical Trial Protocol
 Patient Information leaflet and Informed Consent form
 Investigators Brochure and/or Package Insert
 Signed investigator(s) CV(s) in required format
 Signed declaration by Principal investigator(s)
 Signed joint declaration by Sponsor/National Principal investigator
 Signed declaration by Co- or Sub-investigators
 Signed declaration by regional monitor and/or study coordinator
 Indemnity and Insurance Certificate and/or
 Proof of Malpractice insurance of trialist(s)
 Ethics Committee(s) approval or
 Copy of letter submitted to Ethics Committee(s)
 Electronic copies to be submitted in Microsoft Word format
 Financial declaration by Sponsor and Principle investigator
Bhupal Noble University,Udaipur

6. Clinical Trial Documentation:
Introduction
 All records, in any form (including, but not limited to,
written, electronic, magnetic, and optical records, and
scans, x-rays, and electrocardiograms) that describe or
record the methods, conduct and/or results of a trial, the
factors affecting a trial and the actions taken.
 Such a record is known as, “Document” and process is
“Documentation”
 The trial documents are both a resource and an outcome;
they are the outcome of the study and a resource for the
regulators.
Bhupal Noble University,Udaipur

7. Trial Master File (TMF)
 Guideline E6 states that trail master file should be
established at the beginning of the trail,both at the
investigator/institution site and at the sponsors office.
 A final close-out of a trail only be done when the monitor
has reviewed both the investigator/institution and
sponsor files and confirm that all necessary documents
are in the appropriate files .
 The file maintained at the site is often called,
The Site Master File .
 The file is generally the responsibility of a designated
member of the investigating team at the site of the
monitor at the sponsors office.
Bhupal Noble University,Udaipur

8. Source Documents
 Original documents, data, and records.
 These documents are generally confidential and should
not be made available to all and sundry.
 After the end of the trial period, these docs must be
archived for a very long time.
 ICH guidelines E6 states, Essential documents should be
retained until at least 2 years after last approval of a
marketing application in an ICH region .
 Investigator should ask for a written consent of sponsor to
destroy the documents and this written permission stored
forever.
Bhupal Noble University,Udaipur

9. Essential Documents
 Essential Documents are those documents which
individually and collectively permit evaluation of the conduct
of a trial and the quality of the data produced
 These documents serve to demonstrate the compliance of the
investigator, sponsor and monitor with the standards of
Good Clinical Practice and with all applicable regulatory
requirements.
 Essential Documents also serve a number of other important
purposes.
 These documents are also the ones which are usually audited
by the sponsor's independent audit function and inspected
by the regulatory authority(ies) as part of the process to
confirm the validity of the trial conduct and the integrity of
data collected.
Bhupal Noble University,Udaipur

10. Essential Documents For
Clinical Trials
:The Essential Documents For Clinical Trials are as Follow:
 Investigator's Brochure
 Clinical Study Protocol
 Case Report Form (CRF)
 Informed Consent Form
 Clinical Study Reports
Bhupal Noble University,Udaipur

11. INVESTIGATOR'S BROCHURE (IB):
 List of Abbreviations
 Contents & Summary
 Introduction provides the chemical name (and generic and trade
names, if approved) of the investigational product.
 Physical, chemical and pharmaceutical properties and
formulation of the medicinal product.
 Non-clinical studies & Clinical Studies and their resulkts.
 Conclusions and Guidance for the Investigator
 References (at the end of each section)
 NOTE: The Investigator's Brochure should be reviewed at least
annually and revised as necessary in compliance with a standard
procedures established by drug development company.
Bhupal Noble University,Udaipur

12. CASE RECORD/REPORT FORM (CRF)
 CRF is a paper or electronic document designed to record all the
information for an individual study subject required by the Study
protocol.
All CRF's should include the following data:
 Study title and number;
 Investigator's name;
 Study subject/patient ID (number and initials);
 Inclusion / exclusion criteria;
 Demographic data;
 Detailed description of dosage regimens of investigational drug;
 Concomitant treatment;
 Adverse events (side effects and intercurrent diseases);
 Conclusion on subject's health;
 Investigator's signature and date.
Bhupal Noble University,Udaipur

13. Clinical Study Protocols
 The Guideline ICH E6 defines the protocol as, A document
that describes the objective(s), design, methodology,
statistical considerations, and organization of a trial.
 The protocol usually also gives the background and rationale
for the trail but these could be provided in other protocol
refrenced documents also.
 Appendix II (6) of schedule Y to Drugs and Cosmetic
rules(2005) implies that all clinical trails to be carried out as
per the conditions laid down in the Decleration of Helsinki
(DOH).
Bhupal Noble University,Udaipur

14. Decleration of Helsinki
 “The design and performance of each experimental procedure
involving human subjects should be clearly formulated in an
experimental protocol”.
 “Medical research involving human subjects must conform to
generally accepted scientific principles, be based on a thorough
knowledge of the scientific literature, other relevant sources of
information, and on adequate laboratory and, where appropriate
animal experimentation.”
 “Every medical research project involving human subjects should
be preceded by careful assessment of predictable risks and
burdens in comparison with foreseeable benefits to the subject or
to others”.
Bhupal Noble University,Udaipur

15. Decleration of Helsinki contd.
 “In medical research on human subjects, considerations related to
the well-being of the human subject should take precedence over
the interests of science and society.”
 “In medical research on human subjects, considerations related to
the well-being of the human subject should take precedence over
the interests of science and society”
 “The protocol should be submitted for consideration, comment,
guidance, and where appropriate, approval to a specially
appointed ethical review committee, which must be independent
of the investigator, the sponsor, or any other kind of undue
influence. This independent committee should be in conformity
with the laws and regulations of the country in which the
research experiment is performed”
Bhupal Noble University,Udaipur

16. Decleration of Helsinki contd.
 “The subjects must be volunteers and informed participants in the
research project.”
 “Both authors and publishers have ethical obligations. In
publication of the results of research, the investigators are
obliged to preserve the accuracy of the results. Negative as well
as positive results should be published or otherwise publicly
available”.
 “It is the duty of the physician in medical research to protect the
life, health, privacy, and dignity of the human subject.”
 Note: “Reports of experimentation not in accordance with the
principles laid down in this Declaration, should not be accepted
for publication”.
Bhupal Noble University,Udaipur

17. Parts of Protocol
 Introduction/Abstract
 Objectives
 Background/Rationale
 Eligibility criteria
 Study design/methods (including drug/device info)
 Safety/adverse events
 Regulatory guidance
 Statistical section (including analysis & monitoring)
 Human subjects protection/informed consent
Bhupal Noble University,Udaipur

18. CASE RECORD/REPORT FORM (CRF)
 CRF is a paper or electronic document designed to record all the
information for an individual study subject required by the Study
protocol.
:All CRF's should include the following data:
 Study title and number;
 Investigator's name;
 Study subject/patient ID (number and initials);
 Inclusion / exclusion criteria;
 Demographic data;
 Detailed description of dosage regimens of investigational drug;
 Concomitant treatment;
 Adverse events (side effects and intercurrent diseases);
 Conclusion on subject's health;
 Investigator's signature and date.
Bhupal Noble University,Udaipur

19. INFORMED CONSENT
 Informed consent is a process by which a subject voluntary
confirms his/her willingness to participate in one or another
clinical trial, after having been informed of all aspects of the
study.
 Informed consent should be documented by means of a
written, signed and dated Informed Consent Form (ICF).
:The Subject Should be Informed of the Following:
 the purposes of the trial;
 the methods of the trial;
 the study drug(s) and treatment regimens;
 available alternative treatment(s);
 the potential risks and benefits, and possible discomforts.
Bhupal Noble University,Udaipur

20. Monitoring in Clinical Trial
PURPOSES: SELECTION& QUALIFICATIONS
 The rights and well-being of
human subjects are protected.
 The reported trial data are
accurate, complete, and
verifiable from source
documents.
 The conduct of the trial is in
compliance with the currently
approved
protocol/amendment(s), with
GCP, and with the applicable
regulatory requirement
 Monitors should be appointed by
the sponsor.
 Monitors should be appropriately
trained, and should have the
scientific and/or clinical knowledge
needed to monitor the trial
adequately.
 Monitors should be thoroughly
familiar with the investigational
product(s), the protocol, written
informed consent form and any
other written information to be
provided to subjects, the sponsor’s
SOPs, GCP, and the applicable
regulatory requirement(s).
Bhupal Noble University,Udaipur

21. Monitoring in Clinical Trial contd.
Monitoring Report
 The monitor should submit a written report to the sponsor after
each trial-site visit or trial-related communication.
 Reports should include the date, site, name of the monitor, and
name of the investigator or other individual(s) contacted.
 Reports should include a summary of what the monitor reviewed
and the monitor's statements concerning the significant
findings/facts, deviations and deficiencies, conclusions, actions
taken or to be taken and/or actions recommended to secure
compliance.
 The review and follow-up of the monitoring report with the
sponsor should be documented by the sponsor’s designated
representative.
Bhupal Noble University,Udaipur

22. Bhupal Noble
University,
Udaipur,
Rajasthan