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
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