CLINICAL TRIAL PROTOCOL
Dr Urmila M. Aswar,
Sinhgad Institute of Pharmacy, Narhe,
It is a complete written description and scientific
rationale for a research activity involving human
Writing a Protocol – First steps
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
Who Reads Protocols?
• The protocol language/ content should be
– Other physicians
– IRB members
– Scientific reviewers
– IC for a lay person
• Many NIH programs encourage to use the
protocol templates available eg.
• Following template guidelines can help guide
authors with proper modifications.
Parts of the Protocol
Study design/methods (including drug/device info)
Statistical section (including analysis and
9. Human subjects protection/informed consent
• Objectives should be stated clearly as
hypotheses to be tested.
• Each objective should have a corresponding
discussion in the statistical section.
2. 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.
Background and Rationale
• Double check all citations
• Common mistakes
• Name misspellings (including wrong initials),
wrong journal names, wrong years of
publication, and wrong volume numbers
3. Eligibility criteria- defn.
• Inclusion and exclusion criteria are the
conditions that must be met in 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
Writing Eligibility Criteria for Patient
• Eligibility criteria are the largest barrier to
• 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
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.
4. Eligibility criteria should be straightforward
and unambiguous. Which of these criteria is
1. Pregnant and/or nursing women are not
2. All women of childbearing age are
required to have a negative serum
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.
Failure to write eligibility criteria
• Leads to
Failure to mimic clinical practice
Increased study complexity
Less number of patient getting recruited
• Eligibility criteria given by National Institute of
Neurological Disorders and Stroke’s
participants for a clinical trial titled Study of Brain Activity
During Speech Production and Speech Perception.
• The inclusion criteria specified for the experimental group
were (a) right-handed children and adolescents, (b) native
speakers of American English, and (c) stuttering or
• The comparison (control) group consisted of normally
developing right-handed children and adolescents who
were native speakers of American English.
• Exclusion criteria were (a) language use in the home other
than American English, (b) speech reception thresholds
greater than 25 dB, and (c) contraindications to magnetic
4. 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.
• Parts of the study design section may
Required lab tests
Details of treatment or procedures
Dose scheduling and modification
• 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
• Detailed information for reporting adverse
including reporting to the FDA and/or the sponsor
• Unblinding processes (if applicable)
• Lists of expected adverse events
6. 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.
7.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
o Disclosure of relevant information to prospective
o Comprehension of the information provided to the
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.
The protocol’s informed consent must
• Statement that the study involves research
• Purpose of the research and the length of the
• Description of risks and benefits
• Discussion of alternative therapies
• Confidentiality policy
• Compensation for injury
• Contact for further questions/information
• Statement of voluntary participation
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.
– A document should be checked by automatic
– The document should be proofread.
• Aoccdrnig to a rscheearch at
Cmabrigde Uinervtisy, it deosn't
mttaer in waht oredr the ltteers in a
wrod are, the olny iprmoetnt tihng
is taht the frist and lsat ltteer be at
the rghit pclae.
NIH Guidance on Protocol Writing
• The Office of Human Subjects Research:
• The NCI Investigators’ Handbook:
• It is a comprehensive document summarizing
information about an investigational product
obtained during a drug trial.
• The IB is updated with new information as it
• Compile data relevant to studies of the
investigational drug in human subjects
gathered during preclinical and other clinical
• It sd provide the information for management
of CT and safety during CT
Dose (of the study drug)
Frequency of dosing interval
Methods of administration
Safety monitoring procedures
IB contains Summary of Data and
Guidance for the Investigator
• Provide the investigator with a clear
understanding of the possible risks and
observations, and precautions that may be
needed for a clinical trial
• The information should be based on the
available physical, chemical, pharmaceutical,
pharmacological, toxicological, and clinical
information on the investigational product.
• Should also provide treatment of possible
overdose and adverse drug reactions.
• The IB should be reviewed annually
• Detail guideline is provided in GCP and ICH