Planning and Initiation of a study in Clinical research Documents required for EC submission

1. FUNDAMENTALS OF PRE CLINICAL STUDIES

2. PRE CLINICAL STUDIES
 Preclinical studies or tests are mainly performed in compliance with GLP/GSP guidelines (good
laboratory practice and good scientific practices) to ensure reliability and reproducibility of results.
 The FDA/EMA require supporting basic preclinical data to IND application especially on toxic
effects, safety profile, pharmacokinetics, and pharmacodynamics.
 The data from preclinical trials must be accurate, reliable, and based on the best suitable and
comparable model available to the target population.
 Typically, this means that the IND or drug product must undergo a series of robust tests and
experiments using in vitro, in vivo, ex vivo, and in silico models as per the needs of the focused
indication and regulatory guidelines.
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Performed in- in vitro
- in vivo
- ex vivo
- silico models
To obtain basic information about the safety and
biological efficacy of a drug candidate before testing it in
a final target population, i.e., humans.

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tural_Requirements_for_Bitter_Taste_Receptor_Activation

4. THE CLINICAL DEVELOPMENT PLAN
 The safety and toxicity data generated from pre- clinical studies enables the drug
company to safely initiate clinical trials.
 The scope and duration of these trials will vary widely, depending on the nature of
the drug and its therapeutic application.
 Clinical trials on patients in the different countries are approved and monitored by
different regulatory agencies like:
i) DCGI (Drugs Controller General of India) under CDSCO (Central Drug
Standard Control Organization)- in India
ii) MHRA ( Medicines and Healthcare Products Regulatory agency) advised by
Committee of Safety of Medicines(CAM)- UK
iii) FDA (Food and Drug Administration)- USA
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• A clinical development plan is put together before starting a clinical
trial.
• It is a comprehensive plan designed to map out the development
of a drug compound from early Phase I studies through marketing.
• It consists of the following:
i) Summary of the pre clinical findings
ii) Market research done for the drug
• The clinical development plan usually consists of :
i) Target dates for the studies.
ii) Objectives of each study.
iii) proposed study design for achieving the objectives.
• A clinical development plan covers the studies required for
registration and approval.

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PHASES OF CLINICAL RESEARCH
 Clinical research is done in 4 phases (I, II, III, IV) each designed to address
different questions.
 Research in a particular phase may continue after the drug has progressed to
go further stages of development.
 Based upon the data gathered from the Pre clinical (animal testing) trials, the
sponsor has some estimation of :
- The drugs therapeutic effects and dose levels
- Toxicity profile and dose levels.
 This information is used to design Phase I clinical Trial.

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Only 70% of experimental
drugs pass Phase I clinical
trial
Only 35% of experimental
drugs pass Phase II clinical
trial
Only 25% of experimental
drugs pass Phase III
clinical trial
Only 1 in every 3 drugs
which reaches the market
regains its developmental
costs.

9. PRECLINICAL STUDY MANAGEMENT
 Preclinical Study Management
• Bid solicitation and laboratory selection
• Protocol development
• Data and report review
• On-site study monitoring and preparation
of study monitoring reports
• Preclinical project management
• Central point of contact for study-related
communication
• Development and maintenance of
timelines and budgets for preclinical
programs
 Compliance
• GLP prequalification and auditing
• Data audits to supplement or overlap a
CRO’s inspection
• Standard operating procedures review and
development
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ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS
The essential documents for clinical trials are the following:
• Protocol
• Investigator's Brochure
• Subject Information and Informed Consent Form
• Clinical Study Reports
• Case Report Form (CRF)
• Regulatory Approval
• ERB/IRB/EC Approval

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PROTOCOL
A Document that states the background, objectives, rationale, design,
methodology, ( including methods to deal with AEs, withdrawals etc… along with
statistical considerations of the study.
The following sections should be included in the Study Protocol:
•Introduction (brief description of the problem and treatment
regimen(s))
•Objectives and purposes of the study
•Study duration
•Number of subjects
•Informed Consent
•Opinion of the Ethics Committee
•Subject selection criteria:
• Inclusion criteria
• Exclusion criteria

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•Methodology:
• Study Plan
• Study schedule
• Study Visits
• Study Assessments / Procedures
• Definition of efficacy endpoints
• Treatment cycles
•Safety Reporting
• Adverse events (AEs)
• Serious adverse events (SAEs)
• Abnormal laboratory test values
• Abnormal values of other safety parameters
• Withdrawal from the Study
•Clinical laboratory parameters
•Other safety parameters
•Concomitant medications
•Data analysis
•Appendixes
The following appendixes may be included in the Study Protocol: Patient Information Sheet/Written information
and/or Informed consent form (ICF). Instruction sheet (e.g. for study subjects or study site staff).

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INVESTIGATOR'S BROCHURE (IB):
• Contains pre-clinical and clinical information related to an investigational drug.
• The information should be presented in a concise, simple, objective, balanced form that should
be taken into account during translation.
• The Investigator's Brochure includes - Title Page, which provides the Sponsor's name
- the identity of investigational product (products)
- an edition number and date
- the number and date of the edition it supersedes as well.
The Sponsor may wish to include a Confidentiality Statement instructing to treat the IB as a
confidential document.
PROTOCOL AMENDMENT
Protocol amendment describes major changes to the initial Study Protocol. Protocol amendment
must be again approved by the Ethics Committee.

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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 main principles of Informed consent
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.

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STUDY PROGRESS REPORTS
• The Investigator should provide written reports on study progress to the Ethics
Committee.
• These may be the Interim report on the interim results of the study and their assessment
based on the analysis conducted in the course of the study, or the Final report - full,
comprehensive description of the study including description of investigational materials,
study design, and presentation and assessment of results of statistical analysis.
• Additionally, the Investigator should prepare the written reports on all major changes that
might affect study conduction and/or increase risk to study subjects.
• These are the following: Adverse Event Report or Adverse Drug Reaction Report, Patient
Entry Form(Patient Entry Card/Patient Notification Form) and Patient Withdrawal Form,
Protocol Deviation/Violation Report, Study Termination Report etc.

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CASE RECORD FORM (CRF)
Case record form is a paper or electronic document designed to record all the information for
an individual study subject required by the Study protocol.
The Case record form is used for several purposes:
•to ensure data collection in accordance with the Study protocol;
•to ensure fulfilling of the regulatory authorities' requirements for data collection;
•to facilitate the effective, comprehensive data processing and analysis, results reporting, and to
promote the safety data sharing between the study team and other departments of the
institution.
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.

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Additionally, the CRF's should include special pages to record the
following information:
•past medical history;
•results of physical examination;
•primary and secondary diagnoses;
•relevant previous treatment;
•baseline characteristics, results of interim assessments, evaluation of
efficacy endpoints, laboratory tests, description of study procedures etc.
All CRF's should be legible and suitable for duplication and possible
additional sharing.

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ICH GCP - Essential documents for the conduct of a clinical
trial - ICH GCP
https://www.bing.com/search?q=documents+required+for+initiating+a+study+in+clinical+research&cv
id=7410340d93ad439d9482f96816499bf9&aqs=edge..69i57.18846j0j4&FORM=ANAB01&PC=HCTS&ntr
ef=1

19. ROLES AND RESPONSIBILITIES OF INVESTIGATORS
•By submitting a protocol to the IRB, and being named as the principal investigator (PI) of that
study, the PI is agreeing to assume the overall responsibility for the study conduct. By doing so,
they are agreeing to:
•personally conduct or supervise the research;
•ensure that each individual to whom a task is delegated, is qualified by virtue of education,
training, and experience (e.g., hospital certification, human subjects research training, state license)
to perform each of their delegated tasks;
•protect the rights, safety and welfare of the participants who will be under their care. To do this
they are agreeing that the research :
• is conducted in accordance with all federal regulatory requirements, state law (including IRB
SOPs);
• is conducted in accordance with the IRB approved plan; and
• that they will ensure the accuracy, security and integrity of the research data and the
subsequent analysis of that data. 19

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According to FDA regulations
21 CFR 312.60 An investigator is responsible for ensuring that an investigation is conducted
according to the signed investigator statement (the FDA's 1572 form), the investigational
plan, and applicable regulations; for protecting the rights, safety, and welfare of subjects
under the investigator's care; and for the control of drugs under investigation.
An investigator shall, obtain the informed consent of each human subject to whom the drug
is administered.

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Responsibilities Related to the Conduct of Human Subjects Research
The principal investigator is responsible for ensuring that:
•The protocol is scientifically sound and of scientific and social value;
•There are adequate resources - time, funding, space, staff - to conduct the research;
•They will provide sufficient oversight over all study activities and tasks delegated to others to ensure
that the research is conducted in compliance with all applicable Federal Regulations and
CHOP Policies and Procedures;
•IRB approval will be obtained before starting the study (enrolling subjects);
•After the research is approved, all required reports including: continuing review progress
reports, unanticipated problems, protocol deviations - will be submitted to the IRB, the study sponsor
and the relevant funding agencies in accordance with the CHOP IRB Policies and Procedures and
sponsor/funding agency requirements;

22. WHO IS ELIGIBLE TO BE A PRINCIPAL INVESTIGATOR?
Before you begin to develop a proposal, it is important to be sure you are eligible to serve as a
Principal Investigator.
Anyone holding the following positions may be designated as PIs in applications for sponsored
projects:
1.All Assistant, Associate, and Full Professors
2.All Research Assistant Professors, Research Associate Professors, Research Professors, Extension
Specialists, Clinical Professors, and Senior Research Fellows
3.All Adjunct, Visiting, Lecturers or other faculty who have the approval of their Department and the
approval of the Dean of the relevant School or College. PIs in this category should either include a Co-
PI from appointment types or provide a signed memo where the Chair and Dean shall accept full fiscal
and administrative liability and responsibility for the actions of the Principal Investigator included in
this category.
4.All Post-Doctoral Fellows who have the approval of their Department and the approval of the Dean
of the relevant School or College. The Post-Doctoral Fellow’s mentor must be included as a Co-PI.
5.All Professional Staff also students with the approval of their Department and the approval of the
Dean of the relevant School, College, or Vice Chancellor.
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23. THANK YOU