[QGE031/Ligelizumab] Clinical Trial Protocol [CQGE031C2202 ...
Cinical trial protocol writing
-
Upload
dr-urmila-aswar -
Category
Education
-
view
1.961 -
download
3
description
Transcript of Cinical trial protocol writing
![Page 1: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/1.jpg)
CLINICAL TRIAL PROTOCOL
DEVELOPMENT
AND
INVESTIGATORS BROCHURE
Dr Urmila M. Aswar,
Sinhgad Institute of Pharmacy, Narhe, Pune -41
![Page 2: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/2.jpg)
Protocol writing
It is a complete written description and scientific
rationale for a research activity involving human
subjects.
oObjectives
oDesign
oMethodology
![Page 3: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/3.jpg)
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 lines
![Page 4: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/4.jpg)
Who Reads Protocols?
• The protocol language/ content should be
understood by
–Other physicians
–Nurses/CRAs
– IRB members
–Scientific reviewers
– IC for a lay person
![Page 5: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/5.jpg)
Templates availability
• Many NIH programs encourage to use the
protocol templates available eg.– http://ctep.cancer.gov/guidelines/templates.html
• Following template guidelines can help guide
authors with proper modifications.
![Page 6: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/6.jpg)
Parts of the Protocol
1. Introduction/Abstract
2. Objectives
3. Background/Rationale
4. Eligibility criteria
5. Study design/methods (including drug/device info)
6. Safety/adverse events
7. Regulatory guidance
8. Statistical section (including analysis and monitoring)
9. Human subjects protection/informed consent
![Page 7: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/7.jpg)
1. Objectives
• Objectives should be stated clearly ashypotheses to be tested.
• Each objective should have a correspondingdiscussion in the statistical section.
![Page 8: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/8.jpg)
2. Background and Rationale
• All protocols require a section detailing thescientific rationale for a protocol and thejustification in medical and scientific literaturefor the hypothesis being proposed.
• Introductory section should be organized in alogical, sequential flow.
![Page 9: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/9.jpg)
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
![Page 10: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/10.jpg)
3. Eligibility criteria- defn.
• Inclusion and exclusion criteria are theconditions that must be met in order toparticipate in a clinical trial.
• The most important criteria used to determineappropriateness for clinical trial participationinclude age, sex, the type and stage ofa disease, treatment history, and othermedical conditions.
![Page 11: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/11.jpg)
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
![Page 12: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/12.jpg)
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.
![Page 13: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/13.jpg)
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.
![Page 14: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/14.jpg)
Failure to write eligibility criteria
properly
• Leads to
Failure to mimic clinical practice
Increased study complexity
Increased costs
Less number of patient getting recruited
![Page 15: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/15.jpg)
Example• Eligibility criteria given by National Institute ofNeurological Disorders and Stroke’s for recruitingparticipants for a clinical trial titled Study of Brain ActivityDuring Speech Production and Speech Perception.
• The inclusion criteria specified for the experimental groupwere (a) right-handed children and adolescents, (b) nativespeakers of American English, and (c) stuttering orphonological disorders.
• The comparison (control) group consisted of normallydeveloping right-handed children and adolescents whowere native speakers of American English.
• Exclusion criteria were (a) language use in the home otherthan American English, (b) speech reception thresholdsgreater than 25 dB, and (c) contraindications to magneticresonance scanning.
![Page 16: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/16.jpg)
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.
![Page 17: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/17.jpg)
Study Design• 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
![Page 18: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/18.jpg)
5. Safety
• Adverse effect and side effect are termscommonly associated with drugs. They are usedby nurses and doctors, to refer to undesirableeffects of a medication on a patient.
• The Safety (or Adverse Events) section shouldinclude:
• Detailed information for reporting adverse events,including reporting to the FDA and/or the sponsor
• Unblinding processes (if applicable)
• Lists of expected adverse events
![Page 19: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/19.jpg)
6. The Statistical Section
• The study objectives and study designelements in the statistical section shouldbe described in the Objectives section
• The descriptions and definitions oftoxicities in the statistical section matchthose in the Safety/AE section.
![Page 20: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/20.jpg)
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
![Page 21: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/21.jpg)
Informed Consento Disclosure of relevant information to prospective
research subjects
o Comprehension of the information provided to thesubject
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.
![Page 22: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/22.jpg)
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
![Page 23: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/23.jpg)
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.
– A document should be checked by automatic
software
– The document should be proofread.
![Page 24: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/24.jpg)
• Aoccdrnig to a rscheearch atCmabrigde Uinervtisy, it deosn'tmttaer in waht oredr the ltteers in awrod are, the olny iprmoetnt tihngis taht the frist and lsat ltteer be atthe rghit pclae.
![Page 25: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/25.jpg)
NIH Guidance on Protocol Writing
• Protomechanics:
http://www.cc.nih.gov/ccc/protomechanics/
• The Office of Human Subjects Research:
http://ohsr.od.nih.gov/info/info.html
• The NCI Investigators’ Handbook:
http://ctep.cancer.gov/handbook/index.html
![Page 26: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/26.jpg)
INVESTIGATORS BROCHURE
![Page 27: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/27.jpg)
IB
• It is a comprehensive document summarizinginformation about an investigational productobtained during a drug trial.
• The IB is updated with new information as itbecomes available.
• Compile data relevant to studies of theinvestigational drug in human subjectsgathered during preclinical and other clinicaltrials.
![Page 28: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/28.jpg)
• 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
![Page 29: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/29.jpg)
IB contains Summary of Data and Guidance for the Investigator
• Provide the investigator with a clearunderstanding of the possible risks andadverse reactions, details of tests,observations, and precautions that may beneeded for a clinical trial
![Page 30: Cinical trial protocol writing](https://reader036.fdocuments.in/reader036/viewer/2022062704/5560e528d8b42a086e8b4e01/html5/thumbnails/30.jpg)
• The information should be based on theavailable physical, chemical, pharmaceutical,pharmacological, toxicological, and clinicalinformation on the investigational product.
• Should also provide treatment of possibleoverdose and adverse drug reactions.
• The IB should be reviewed annually