CLINICAL TRIAL PROTOCOL DEVELOPMENT

1. CLINICAL TRIALPROTOCOL
DEVELOPMENT
PRESENTED BY,
SACHIN.C.P
M. PHARM. (SEM – I)
DEPT. OF PHARMACEUTICS
RGIP TRIKARIPUR
1

2. Protocol writing
It is a complete written description and scientific
rationale for a research activity involving human
subjects.
o Objectives
o Design
o Methodology
2

3.  The PI must know the answers for
 Is it reasonable? Do we have the resources?
 What are the significant risks?
 Do we have the patient population?
 Associate Investigator/ outside investigators
may be included.
 Should be able to write the whole CT in few
lines
3

4. Who Reads Protocols?
• The protocol language/ content should be
understood by
–Other physicians
–Nurses/CRAs
–IRB members
–Scientific reviewers
–IC for a lay person
4

5. PARTS OF THE PROTOCOL
1. TITLE PAGE
2. SIGNATURE PAGE
3. CONTENT PAGE
4. LIST OF ABBREVIATIONS
5. INTRODUCTION/ABSTRACT
6. OBJECTIVES
7. BACKGROUND/RATIONALE
8. ELIGIBILITY CRITERIA
9. STUDY DESIGN/METHODS (INCLUDING DRUG/DEVICE INFO)
10. SAFETY/ADVERSE EVENTS
11. REGULATORY GUIDANCE
12. STATISTICAL SECTION (INCLUDING ANALYSIS AND
MONITORING)
13. HUMAN SUBJECTS PROTECTION/INFORMED CONSENT 5

6. 1. TITLE PAGE
• Title page introduce the document ,its title, precise
number , sponsor and author to the reader.
• Protocol identifying number and date. Any
amendment should also bear the amendment
number and date.
• The protocol number must clearly indicate the
version number , whether it is final or draft and date
of this version.
6

7. Title page should includes :
1. Full title should include summary study design, medicinal
products ,nature of treatment (eg : treatment, prophylaxis
and diagnosis) comparator placebo , indication patient
population setting (eg : in-patient, outpatient) Randomised
double bind multiple studies.
2. Name and address of sponsor and monitor. Sponsor names
and list of responsibilities with agreed allocations
3. Name and address of the person authorised to sign the
protocol and protocol amendment for the sponsor. Generally,
chief investigator for multicentric trial or principle
investigator for single center trials.
7

8. 4. Name ,title , address and telephone number of the sponsor
medical expert for the trial
5. Name and title of the investigator who is responsible for
conducting the trial , and the address and telephone number
of the trial site.
6. Name , title , address and telephone number of the qualified
physician who is responsible for all trial site related medical
decisions.
7. Name and address of the clinical laboratory and other
medical and/or technical and/or institutions involved in the
trial.
8

9. 2. SIGNATURE PAGE
• Signature page of all healthcare professionals in the trial
including contact details of participating site, sponsor and
sponsor medical advisor if not already given above.
3. CONTENT PAGE
• This help navigation through the document by large number of
different people that will be needed throughout the life of the
trial.
9

10. 4. LIST OF ABBREVIATIONS
• All abbreviations used should be listed and defined. Accepted
international medical abbreviations should be standardised
within each project.
5. INTRODUCTION / ABSTRACT
• 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.
10

11. 6. Objectives
clearly as• Objectives should be stated
hypotheses to be tested.
• Each objective should have a corresponding
discussion in the statistical section.
11

12. 7. Background and Rationale
• 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.
12

13. • Double check all citations
• Common mistakes
• Name misspellings (including wrong initials),
wrong journal names, wrong years of
publication, and wrong volume numbers
13

14. 8. Eligibility criteria- definition.
• Inclusion
conditions
and exclusion criteria
that must be met in
are the
order to
participate in a clinical trial.
• The most important criteria used to determine
appropriateness for clinical trial participation
include age, sex, the type and stage of a
disease, treatment history, and other medical
conditions.
14

15. Writing Eligibility Criteria for
Patient
• Eligibility criteria are the largest barrier to
clinical trials.
• There is no guideline for writing these criteria
• Poorly written or poorly conceived criteria
may affect the scientific validity of CT.
• Reasons for imposing eligibility criteria
includes scientific rationales, safety concerns,
regulatory issues, and practical considerations
15

16. The points to be considered to write
a good eligibility criteria
1. The number of eligibility criteria should be
kept to a minimum.
2. Criteria should include only those
absolutely necessary to ensure scientific
validity and patient safety.
3. Eligibility criteria should be clearly defined
and verifiable by an external auditor.
16

17. 4. Eligibility criteria should be straightforward
and unambiguous. Which of these criteria is
better understood?
1. Pregnant and/or nursing women are not
eligible.
2. All women of childbearing age are
required to have a negative serum
pregnancy test.
3. Nursing women are not eligible for this
study. All women of childbearing potential
must have a negative serum pregnancy test
within 2 weeks of study enrollment. 17

18. Failure to write eligibility criteria
properly
• Leads to
Failure to mimic clinical practice
Increased study complexity
Increased costs
Less number of patient getting recruited
18

19. 9. Study Design
• 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 for the participating site.
19

20. • Parts of the study design section may
include:
 Initial evaluations
 Screening tests
 Required lab tests
 Details of treatment or procedures
 Device specifications
 Dose scheduling and modification
 Calendars
20

21. 10. Safety
• Adverse effect and side effect are terms
commonly associated with drugs. They are used
by nurses and doctors, to refer to undesirable
effects of a medication on a patient.
• The Safety (or Adverse Events) section should
include:
• Detailed information for reporting adverse events,
including reporting to the FDA and/or the sponsor
• Unblinding processes (if applicable)
• Lists of expected adverse events
21

22. 11. The Statistical Section
• The study objectives and study design
elements in the statistical section should
be described in the Objectives section
• The descriptions and definitions of
toxicities in the statistical section match
those in the Safety/AE section.
22

23. 12.Human Subjects Protection
• This section includes discussion of:
– Subject selection and exclusion
– Proposed methods of patient recruitment
– Minority representation
– Recruitment (or exclusion) of special subjects,
including vulnerable subjects
– Lists of potential risks and benefits, including
justification for risks
23

24. Informed Consent
o Disclosure of relevant information to prospective
research subjects
o Comprehension of the information provided to the
subject
o Voluntary agreement of the subject.
The protocol’s informed consent must
• Be thorough and complete
• Be written in simple, nontechnical language
• Be carefully worded to avoid complexity.
24

25. 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/information
• Statement of voluntary participation
25

26. Tools for Better Writing:
Proofreading
Working too long on a protocol may habituate eyes
and brains to mistakes, simply because they’ve
been there all along.
Spell-checkers, etc.
by automatic– A document should be checked
software
– The document should be proofread.
26

27. 27