Clinical trail protocol and development

 As per ICMR, A clinical trail is any research/study that
prospectively assigns human participants or groups of
humans to one or more health-related interventions to
evaluate the effects in health outcomes.
 The intervention could be drugs, vaccines, biologics,
phytopharmaceuticals, radiopharmaceuticals, diagnostic
agents, medical devices, surgical techniques etc…..
 Clinical trails are usually well controlled studies.
 At present, Due to huge patient load, wide variety of
diseases, low operational cost, sufficient infrastructure
India is a hub for clinical trails.

 DRUGS AND COSMETICS ACT (schedule Y):
Requirements and guidelines for permission
to import and / manufacture of new drugs for sale or to
undertake clinical trails.
 ICH GUIDELINES-E6(R2):
Good clinical practice addendum to ICH,
clinical trail protocol and protocol amendments.
 INDIAN COUNCIL OF MEDICAL RESEARCH:
National ethical guidelines for biomedical
and health research involving human participants,
these deals with the ethical consideration.

It is housed at the National Institute of
Medical Statistics, ICMR, New Delhi
Trail registration is purely online, paperless
process and free of charge
The CTRI software application was modified
and implemented on 15 march 2011
It makes the information available to both
public and health care professionals
To increase awareness and accountability of
all the participants of the clinical trails and
also for public access

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

 It is acomplete written description and scientific
rationale for a research activity involving human
subjects.
a)Objectives.
b)Design.
c)Methodolgy.
 The PI must know the answers for;
# Is it reasonable? Do we have the resources?
# What are the significant risks?
# Do e have the patient population?
 Should be able to write whole CT in few lines.

 The written protocol language / content should be
understood by:
 Other physicians
 Nurses
 CRAs (Clinical Research Associates)
 Scientific reviewers
 Board members
 Press and Journals
 IC (Informed Consent) for a lay person

1. Title page.
2. Signature page.
3. Content page.
4. List of abbrevations.
5. Introduction/Abstract.
6. Objectives.
7. Background/Rationale.
8. Eligibilty Criteria.
9. Study design/Methods.
10. Safety/Adverse events.
11. Regulatory Guidence.
12. Statistical section.
13. Human subjects protection.

 Title page intoduce the document, its title, precise, number,
sponsor and author to the reader.
 Protocol identifying number and date.
 Full title page should include summary, study design,
medicinal products, nature of treatment, patient population
setting indication (in-patient, out-patient), randomised
double multiple studies.
 Name and address of sponsor and monitor. Sponsor names
and list of responsibilities ith agreed allocations.
 Name and address of the person authorised to sign the
protocol. Generally, chief investigator for multicentric trial
or principle investigator for single centre trails.
 Name and address of the clinical laboratory and other
institutions involved in the trail.

 Signature page should include signatures of all health
care professionals and others, who participated in the
clinical trial.
 Signature page should also include contact details of
participating site, sponsor and sponsor medical advisor.
 signature of sponsor responsible persons not named on
the cover page.

 This help navigation through the document by large
number of different people that will be needed
throughout the life of the trial.
 In contet page, Table of in-text tables, Table of in-text
figures should be separetly written.
 Table of in-text tables contains schedule of assessments,
instruction of trail periods,sampling collection schedule,
heamotology assessments, bilogical assessments,
estimated blood sample volumes per subject.
 Table of in-text figures contains schematic chart of trial
design.

 All abbrevations should be listed and defined.
 Accepted international medical abbrevations should be
standardised within each project.
EXAMPLES:
1. DBP (Diastolic Blood Pressure)
2. CRU (clinical Research Unit)
3. ICF (Informed Consent Form)
4. SBP (Systolic Blood Pressure)
5. MDRD (Modification of Diet in Renal Disease)
6. SEM (Standard Error of the Mean)

 This summary should be only one to two pages long.
 It should give the reader sufficient information to
understand the rationale for the trial, its objective and the
methods that will be used to achieve these objective.
 Introduction/Abstarct shoul be;
1. PRECISE (strictly conforming to a pattern, standard)
2. CONCISE (giving a lot of information clearly and in a
few words)
3. SPECIFIC (descriptive should be noted round the
point)

 Objective should be stated clearly as hypothesis to be
tested.
 Each objective should have a corresponding discussion in
the statistical section.
A) PRIMARY OBJECTIVES:
 The primary research objective should be an abridged
(shortened) form of the problem statement.
B) SECONDARY OBJECTIVES:
 The secondary objectives should try to establish a
relationship beteen the different variables of a research
topic and suggest possible recommendations for dealing
with the main research problems.

 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.
 Introductory section should be organized in a logical,
sequential flow.
 Double check all citations.
 common mistakes:
 Name misspellings (including rong initials)
 Wrong journal names
 Wrong years of publication
 Wrong volume numbers

 Inclusion and Exclusion criteria are the conditions that
must be met in order to participate in a clinical trial.
A) INCLUSION CRITERIA:
Inclusion criteria contain only those items that
define the target population desired for study, within the
limits of known safety coverage, should generally allow
inclusion of the broadest representation of the population for
intended use, but usually not beyond.
B) EXCLUSION CRITERIA:
Exclusion criteria are defined as features of the
potential study participants who meet the inclusion criteria
but present with additional characteristics that could interfere
with the success of the study or increase their risk for an
unfavorable outcome.

 Eligibilty criteria are the largest barrier to clinical trails.
 There is no guideline for writing these criteria.
 Poorly written or poorly conceived criteria may affect the
scientific validity of CT.
THE POINTS TO BE CONSIDERED TO WRITE A GOOD
ELIGIBILITY CRITERIA:
 The number of eligibilty criteria should be kept to a
minimum.
 Criteria should include only those absolutely necessary to
ensure scientific validity and patient safety.
 Eligibilty criteria should be clearly defined and verifiable
by an external auditor.
 Eligibility criteria should be straightforward and
unambigous (precise).

 The study design section of the protocol should contain
a stepwise description of all procedures required by the
study.
 A good study design section includes sufficient
information foe the participating size.
 Parts of the study design section may include:
 Initial evaluations.
 Screening tests.
 Required lab tests.
 Details of treatment.
 Device specifications.
 Dose scheduling and monitorng

 Adverse effect and sid effect are terms commonly
associated ith drugs.
 They are used by nurses and doctors, to refer to
undesirable effects of a medication on a patient.
 The safety section or adverse events section should
include;
 Detailed information for reportin adverse events,
including reporting to the FDA and the sponsor.
 If applicable, Unblinding process (code-breaking).
 Lists of expected adverse events.

 The study objectives and study design elements in the
statisitical section should be described in the objectives
section.
 The descriptions and defintions of toxicities in the
statistical section match this in the safety or adverse
event section.
 Elements included in the statistical section;
 Efficasy analyses.
 Safety analyses.
 Missing value handling and subject evaluability.
 Statistical adjustments for multiple endpoints.

 A protocol ithout the human-subject protections section
ill not be accpted for review by the IRB (Institutional
Review Board).
 This sction includes discussion of:
 Subject selection and exclusion.
 Proposed methods of patient recruitment.
 Recruitment or exclusion of spcila subjects, including
vulnerable subjects.
 Lists of potential risks and benefits, including
justification for risks.

 Informed consent process ensures the individuals
autonomy, to voluntarily participate in a trail.
 The protocol’s informed consent must provide;
 Statement that the study involves research.
 Purpose of the research and the length of the study.
 Description of risks and benefits.
 Discussion of alternative therapies.
 Confidentiality policy.
 Compensation for injury.
 Contact for further questions and information.
 statement of voluntary participation.

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