Protocols for Clinical Research

1. Presented By
Dr. Puneshwar Keshari,
1st Year PG Scholar,
Guided By
Dr. Prakash L. Hegde
Professor
DEPT. OF DRAVYAGUNA

2.  Definition of Research
 Clinical Research and Clinical Trial
 Clinical Research Protocol
 Why Protocol
 Parts of Protocol
 Formats of Clinical Research Protocol
 Clinical Research in Ayurveda
 Discussion
 Conclusion
 References

3.  Research is
Systematic collection,
Analysis and
Interpretation of data
to answer a certain
question or solve a
problem

4. Clinical research Clinical trial
Branches of medical
science
Part of clinical research
Systematic, observational
and biomedical studies
Systematic experimental
biomedical studies
Ultimate goal is to improve
the quality of life
To evaluate the
effectiveness and safety of
medications or medical
devices or biologics
CLINICAL RESEARCH &
CLINICAL TRIAL

6. “ A complete written description of,
and scientific rationale for, a
research activity involving human
subjects.”

7. To clarify the research question
To compile existing knowledge
To formulate a hypothesis and objectives
To decide about a study design
To clarify ethical considerations
To apply for funding
To have a guideline and tool for the research team

9. • Introduction
• Abstract
• Objectives (including study scheme)
• Background
• Rationale
• Eligibility criteria
• Study design/methods (including drug/device info)
• Criteria For Evaluations
• Study Treatments
• Clinical Assessment

10.  Clinical Laboratory Measurements
 Evaluations by visit
 Adverse experience reporting and
Documentation
 Discontinuation and Replacement of subjects
 Protocol violations
 Statistical section (including analysis and
monitoring)
 Administrative, Ethical , Regulatory
Considerations
 Reference/ Appendices
 Publication

11. Study Subject / hypothesis
should be clearly identified
and briefly described in
introduction.

12. Abstract is a summary of the
information in a document.
Abstract must be:
Accurate - which correctly
reflects the purpose and content
of manuscript.
Concise and specific – to make
sentence informative and as
possible as brief.
Non evaluative – to report
information objectively

13. Objectives should be clearly mentioned as hypotheses to be
tested.
It should have a corresponding discussion in the statistical
section.
Objectives are of two types:
Primary objective &
Secondary objective

14.  All protocols require a section detailing
the scientific rationale for a protocol
and the justification in medical and
scientific literature for the hypothesis
being proposed.

15.  Describe why it makes sense to study this product
in this patient population or in the event of an
observational study, why the information is
needed.
 Risk / benefit assessment – how the specific risks
of the product will be alleviate in the study and
why the potential benefits outweigh the risks
should be clearly mentioned

16. Subjects with a diagnosis of the specific disease
intended to take in the study, who meet the
inclusion and exclusion criteria will be eligible for
participation in this study.
Reasons for imposing eligibility criteria can
include scientific rationales, safety concerns,
regulatory issues, and practical considerations.

17. The number of eligibility criteria should be kept
to a minimum.
Criteria should include only those absolutely
necessary to ensure scientific validity and patient
safety.
Eligibility criteria should be clearly defined and
verifiable by an external auditor.

18. The study design section of the protocol should contain
a stepwise description of all procedures required by
the study.
• Parts of the study design section may include:
– Initial evaluations
– Screening tests
– Required lab tests
– Details of treatment and supplementary procedures
– Agent information or device specifications
– Dose scheduling and modification
– Calendars

19. Types of study design used in clinical research
Observational study
Interventional study
Descriptive study
Analytical study
Cross sectional study
Cohort study

20. • Study characteristics
• Type of study design to be used
• The way in which study will be conducted
Single center
Double blind
Placebo control
Randomized / non randomized

21. Methodology
Sampling
Collection of data
Statistical analysis
Merits and demerits of particular study

22. Safety evaluation
Evaluation of LFT, RFT etc.
Incidence of adverse events
The Safety (or Adverse Events) section should include:
Detailed information for reporting adverse events
Lists of expected adverse events

23. Concurrent Medication
Formulation of Test and control products
Packaging and labeling
Dose/Dosage regimen
Dispensing
Administration
Supply/Storage
Complications

24. All subjects should be maintained on the same
medications throughout the entire study period, as
medically feasible, with no introduction of new
chronic therapies.
Standard therapy for specific disease is allowed except
for treatments noted in the exclusion criteria.

25. Identify the test and control product, manufacturer, specify
the formulation of the test article. If drug must be
reconstituted or otherwise prepared indicate in this section
Control Test
Active ingredient,
mg/ml
Other ingredient,
mg/ml
pH

26. Brief explanation of how the drug will be packed
and labeled and by whom.
It should also explain how labeling will maintain
blinding for blinded studies.

27. Information of
Dose
Route of administration
Dosing schedule
Optimal timing between doses
Adjustments for weight, age, meals and other pertinent
information and
Treatment periods

28. Dispensing
Administration instructions
Supply of drug at the site
Storage
Study drug accountability
Measures of treatment compliance

29. Concomitant medications
all concomitant medications and concurrent therapies will be
documented.
Demographics
date of birth, gender, race
Medical history
Physical examination
Vital signs
Other clinical procedures

30. Adverse events
Duration (start /stop dates and times)
Severity/ grade
Mild
Moderate
Severe
Life threatening Information regarding occurrence of
adverse events will be captured throughout the study
and reported accordingly.

31. Treatment and relation of adverse experience to study
drug will be recorded on the case report form as
Definitely
Probably
Possibly
Unrelated

32. Hematology
Bio-chemistry profile
Pregnancy test
Urinalysis
Pharmacokinetic measurements
Others

33. VISIT 1
(Day/Week/M
onth )
VISIT 2
(Day/Week/
Month )
VISIT 3
(Day/Week/M
onth )
VISIT 4
(Day/Week/M
onth )
VISIT 5
(Day/Week/M
onth )
Informed
Consent
X
Medical History X
Complete
Physical Exam
X X
Abbreviated
Physical Exam
X X X
Height X X X X X
Weight X X X X X
Vital Signs X X X X X
Oximetry X X X X X
Spirometry X X X X X
Pharmacokinetic
s
X
Chemistry X X X

34. VISIT 1 VISIT 2 VISIT 3 VISIT 4 VISIT 5
Pregnancy Test (Urine or Serum) X X X
Hematology X X X
ESR X X X
C-Reactive Protein X X X
Urinalysis X X X
Randomization X
Dispensing or Administration of
Study Drug
X X X X
Counting of Returned Study Drug X X X X
Initiate Subject Diary X
Subject Diary Review X X X X
Concomitant Medication Review X X X X X
Adverse Experiences

35. All subjects are free to withdraw from participation
at any time, for any reason, specified or
unspecified and without prejudice
Researcher should keep proper record of
Time
Reason
Adverse experience
Consent from to withdraw

36. A protocol violation occurs when the subject,
investigator or sponsor fails to adhere to significant
protocol requirements affecting the inclusion,
exclusion, subject safety and primary endpoint
criteria.

37. Protocol violations of the study include
• Failure to meet inclusion / exclusion criteria
• Use of a prohibited concomitant medication
• Failure to follow good clinical practice.

38. To ensure the continued scientific
validity and merit of the study

39. The data which may be subjected to statistical
analysis may be specified with specific
processes tests, formulae, and which may be
adopted for analysis of data, may be proposed
in blue prints in advance.
Sample size should be clearly mentioned and
reasons for selecting such number for study
also be clearly defined.

40. Data will be entered into a validated database
All procedures for the handling and analysis of
data will be conducted by using good computing
practices.
DATA COLLECTION, ANALYSIS
RETENTION & MONITORING

41. The investigator is responsible for all information
collected on subjects enrolled in this study.
All data collected during the course of this study must
be reviewed and verified for completeness and
accuracy by the investigator.
A copy of case report form should be with investigators
at the completion of study.

42. The study should be conducted according to
Declaration of Helsinki
Protection of Human Volunteers
Institutional Review Board
Institutional Ethics Committee
Obligation of Clinical Investigators
Good Clinical Practices

43. The protocol, consent form and protocol
amendments should be reviewed and approved by
the IRB/IEC.
Serious adverse experiences regardless of causality
should be reported to the IRB/IEC.

44. Informed consent should be prepared in accordance
with the declaration of Helsinki, ICH GCP
(International council for harmonization good clinical
practices), FDA (Food and Drug Administration,
USA), health insurance portability and accountability
act (HIPAA) and local regulations.

45. A proper executed, written, informed consent will
be obtained from each subject prior to entering the
subject into the trial.
Information should be given in both oral and
written form in their native language to subjects/
or their legal representatives about the study.

46. In order to maintain subject
confidentiality, only a site number,
subject number and subject initials will
identify all study subjects on CRFs and
other documentation.

47. All laboratory specimens, evaluation forms,
reports and other records should identified by a
coded number and initials only
All study records should be kept in a locked file
cabinet

48. Code sheets linking a patients name to a patient
identification number should be stored separately in
another locked file cabinet
Clinical information should not be released without
written permission of the subjects, except as necessary
for monitoring by the authorized agency.

49. All references cited in the protocol and/or relevant
to the study should be listed properly
Supplemental documents such as data collection
form, surveys, questionnaires, advertisements, and
flyers should be included to the protocol.

50. The publication or presentation of any study results
should be according to the privacy laws, agreement
with sponsor, health insurance portability and
accountability act.

51. Article

52. Abstract:
Cosmetic Dermatology is a growing subspecialty. High-
quality basic science studies have been published; however,
few double-blind, randomized controlled clinical trials,
which are the major instrument for evidence-based
medicine, have been conducted in this area. Clinical
research is essential for the discovery of new knowledge,
improvement of scientific basis, resolution of challenges,
and good clinical practice. Some basic principles for a
successful researcher include interest, availability,
persistence, and honesty. It is essential to learn how to
write a protocol research and to know the international
and national regulatory rules.

53. A complete clinical trial protocol should include question,
background, objectives, methodology (design, variable
description, sample size, randomization, inclusion and
exclusion criteria, intervention, efficacy and safety
measures, and statistical analysis), consent form, clinical
research form, and references. Institutional ethical review
board approval and financial support disclosure are
necessary. Publication of positive or negative results should
be an authors' commitment.
 Keywords: Clinical protocols; Clinical trial; Comparative
study; Cosmetics; Epidemiologic research design; Research
design

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57. DISCUSSION

58. Research as may be defined as attempt to find out/
discover facts in a systematic and scientific manner
with statistical support.
Clinical research refers to the entire bibliography of
drug/device/biology or in fact any test article from it’s
inception in the lab to it’s introduction to the
consumer market and beyond.
Clinical trials are parts of clinical research in which
experiments are done on human participants.

59. Clinical research must be always conducted within
the frame work of prevailing relevant laws of
country & state.
A properly planned & executed clinical study is a
powerful experiment technique for assessing the
efficacy of an intervention.

60. Protocol is a systematic & complete Performa of
research activity, needed for clarify research question
& ethical consideration & useful to applying for
funding.
Problem identification, literature review, developing
research question and statistical hypothesis are the
main steps for preparing research protocol.

61. Project summary, general information, rationale and
background, references, study goals and objectives, study
design, methodology, safety considerations, follow up, data
management and statistical analysis, quality assurance,
expected outcome, dissemination of results and
publication policy, duration, ethical considerations, budget
and other support projects are the parts of protocol .
Researcher can modify the content according to the types
of study,

62. Chikitsha chatushpada dealt in Charak samhita and their
individual characteristics of each pada should be
considered as requirements and protocols for clinical
research .
Rog and Rogi Pareeksha vidhi and Pareekshya vishay
should be considered as methodology for research
protocol.

63. Clinical research protocol is a
systematically structured scientific
framework of guidelines for
clarifying research question.
Proper and appropriate solution
should only be drawn by applying
appropriate Protocol in clinical
research study.

65. Protocol Number:
Version Date:
Investigational Product:
IND Number:
Development Phase:
Sponsor: Name (please note – for academic studies, the sponsor is
the Investigator, not the funding agency.)
Address, City, State
Funding Organization:
Principal Investigator: Name:
Telephone: Fax: E-mail:
Medical Monitor: Name:
Telephone: Fax: E-mail:
Coordinating Center: If applicable
SPONSOR NAME
Clinical Research Protocol
PROTOCOL NAME

66. Approval:
PI or Sponsor Signature (Name and
Title)
Date
This confidential information about an investigational product
is provided for the exclusive use of investigators of this product
and is subject to recall at any time. The information in this
document may not be disclosed unless federal or state law or
regulations require such disclosure. Subject to the foregoing,
this information may be disclosed only to those persons involved
in the study who have a need to know, with the obligation not to
further disseminate this information.

67. PROTOCOL AGREEMENT
I have read the protocol specified below. In my formal capacity as Investigator,
my duties include ensuring the safety of the study subjects enrolled under my
supervision and providing [Sponsor Name] with complete and timely
information, as outlined in the protocol. It is understood that all information
pertaining to the study will be held strictly confidential and that this
confidentiality requirement applies to all study staff at this site. Furthermore, on
behalf of the study staff and myself, I agree to maintain the procedures required
to carry out the study in accordance with accepted GCP principles and to abide
by the terms of this protocol.
Protocol Number: Number
Protocol Title: Title
Protocol Date: TBD
Investigator Signature Date
Print Name and Title
Site #
Site Name
Address

68. TITLE
SPONSOR
FUNDING
ORGANIZATION
NUMBER OF SITES
RATIONALE This should be very brief – 2 paragraphs or so, just
highlighting why it makes sense to study product X in
these patients and that there is a medical need.
STUDY DESIGN This is a randomized, double-blind, placebo-controlled
phase 2 study.
PRIMARY OBJECTIVE
SECONDARY
OBJECTIVES
PROTOCOL SYNOPSIS

69. NUMBER OF SUBJECTS
SUBJECT SELECTION
CRITERIA
Inclusion Criteria:
Exclusion Criteria:
TEST PRODUCT, DOSE, AND
ROUTE OF
ADMINISTRATION
Product XX at XX dose
Product will be administered every XX hours (or days) for X length
of time. Describe administration (orally, IV, or by inhalation). If
inhalation describe delivery system.
CONTROL PRODUCT, DOSE
AND ROUTE OF
ADMINISTRATION
Product XX (indicate if comparator or placebo) at XX dose
Product will be administered every XX hours (or days) for X length
of time. Describe administration (orally, IV, or by inhalation) If
inhalation describe delivery system.
DURATION OF SUBJECT
PARTICIPATION AND
DURATION OF STUDY
Subjects will be on study for up to 28 days
Screening: up to 7 days
Treatment: 5 days (subjects to be admitted to the hospital)
Follow-up: 16 days
The total duration of the study is expected to be XXX. XXX months
for subject recruitment and XXX for final subject follow-up.

70. E
CONCOMMITANT
MEDICATIONS
Allowed:
Prohibited:
EFFICACY EVALUATIONS
PRIMARY ENDPOINT
SECONDARY ENDPOINTS
OTHER EVALUATIONS PK, research lab evaluations, etc., would go here
SAFETY EVALUATIONS Change in clinical safety labs from baseline to XXX
Incidence of adverse events
PLANNED INTERIM
ANALYSES
Fill in details of DMC. Please note: if this is a NIH-funded study,
all references should be “DSMB”; for non-NIH funded studies,
refer to the” DMC.” Sample text: When approximately 50% of
patients have completed the study through Visit X, an interim
analysis for safety will be conducted by an independent data
monitoring committee. Serious adverse events will be monitored by
the committee on an ongoing basis throughout the study.
STATISTICS
Primary Analysis Plan
Describe plan for analyzing the primary endpoint.
Rationale for Number of
Subjects

71. WHO recommended format for clinical research
protocol 1 and2
CCRAS Research Policy
 Research Methodology- C.R. Kothari .Gaurav Garg
 Research Methodology and Medical Biostatistics –
DR.S.M. Sarpotdar, Dr. Santosh Bhor
 Charak Samhita
Writing Research Protocol- Manubhakta
PROTOCOL TEMPLATE- University of
California, Sanfrancisco.