Preparation of protocol
- 1. Preparation of Protocol Rushikesh S Tidake M.Pharm Sem ll Pharmacology Rajarshi Shahu College of Pharmacy Buldana 1/18
- 2. Contents Introduction Types of Clinical trial Phases of Clinical trial Clinical trial Protocols 2/18
- 3. Introduction •Clinical trials are sets of tests in medical research & Drug Development that generate safety and efficacy data for health intervention (Eg. drugs,diagonistics,devices,therapy protocols) •They are conducted only after satisfactory information has been gathered on the quality of nonclinical safety ,and health authority/ethics committee approval is granted in the country where approval of the drug or device is sought. •The clinical trial design & objectives are written into a document called a clinical trial protocol. It is a document that states background , objectives , rationale , design , methodology and statistical consideration of the study .It also states the condition under which the study shall be performed and managed . 3/18
- 4. Types of Clinical trial : 1) Prevention trial : • Look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning .This approaches may include medicines vitamins , minerals , or lifestyle changes . 2) Screening trial : Test the best way to detect certain disease or health conditions. • Assess the safety and effectiveness of a different dose of a medication than is commonly used ( eg. 10mg dose instead of 5mg dose ) • Compare the effectiveness with patients with a specific disease of two or more already approved or common interventions for that disease . 4/18
- 5. 3) Diagnostics trial : •Conduct to find better tests or procedures for diagnosing a particular disease or condition. In a clinical trial, the investigator first identifies the medication/device be tested. Then the investigator decides what to compare it with and what kind of patients might benefit from the medication/device. 4) Treatment trial •Test experimental treatment , new combination of drugs , or new approaches to surgery or radiation therapy . 5) Quality of life trial •Explore ways to improve comfort and quality of life for individual with a chronic illness. 6) Compassionate use trial •Provide experimental therapeutics prior to final FDA approval to patients whose optional with other remedies have been unsuccessful. Usually case by case approval must be granted by FDA for such exception. 5/18
- 6. Phases of clinical trial : Clinical trial involving new drugs are commonly classified into four phases . Each phase of the drug approval process is treated as a separate clinical trial . The drug-development process will normally proceed through all four phases over many years . If the drug successful passes through Phases 0,1,2& 3 , it will usually be approved by the national regulatory authority for use in general population. •Phase 0 : Pharmacodynamics & Pharmacokinetics •Phase 1 : Screening for safety •Phase 2 :Establishing efficacy of drug usually against a placebo •Phase 3 : Final confirmation of safety & efficacy •Phase 4 : Provide additional information about benefit & risk 6/18
- 7. Clinical trial Protocols : 1. General Information 2. Objectives and Justification 3. Ethical Consideration 4. Study Design 5. Inclusion , Exclusion & Withdrawal of subjects 6. Handling of product 7. Assessment of Efficacy 8. Assessment of Safety 9. Statistics 10. Data handling and Management 11. Quality control and Quality assurance 12. Finance And Insurance 13. Publication policy 14. Evaluation 15. Supplementation and appendices 7/18
- 8. 1.General Information •Protocol title, protocol identifying number and date. All amendments number and date(s) •Name , address & contact number of the sponsor and the monitor /CRO •Name and title of the persons authorised to sign the protocol amendments for the sponsor •Name , title, address and contact number of sponsor’s medical expert for the study •Name ,title , address and contact number of the investigators who are responsible for conducting the study ,along with their consent letters • Name ,Address & contact number of the institutions – clinical laboratories and / or other medical & technical departments along with the particulars of the head of institutions and the relevant department. 8/18
- 9. 2. Objectives & Justification : •Aims & objectives of the study , indicating the Phase to which the study corresponds •Name and description of the investigational products •A summary of findings from non-clinical studies that potentially have clinical significance & from clinical studies that are relevant to the study •Summary of the known & potential risks and benefits if any ,to human objects •A statement that the study will be conducted in compliance with protocol , GCP and applicable regulatory requirements •Descriptions of the inclusions & exclusions criteria of the study population •References to literature & data that are relevant to study & that provide background for the study . 9/18
- 10. 3. Ethical consideration : •General ethical consideration related to study •Description of how patients/healthy volunteers will be informed and how their consent will be obtained •Possible reasons for not seeking informed consent. 4. Study Design : •The scientific integrity of the study & the credibility of the data from the study depend substantially on the study design. Description of the study design should include •Specific statement of primary & secondary end points ,if any ,to be measured during the study •Description of the type of the study ,study design ,blinding technique ,randomisation & placebo controlled . •A schematic diagram of the study design , procedures and stages •Medications/treatment permitted & not permitted before and or during the study. 10/18
- 11. •A description of the manner of packaging & labelling of the investigational product. •Duration of the subject participation and a description of the sequence of all study period including follow up the study •Proposed date of initiation of the study •Maintenance of study treatment randomisation codes & procedures for breaking codes. •Documentation of any decoding that may occur during the study. •Procedure for monitoring subjects compliance. 5) Inclusion , Exclusion & Withdrawal of Subjects • Subject inclusion criteria : Specification of the subjects(patients/Healthy volunteers ) including age , gender , ethic groups , Prognostic factors , Diagnostic admission criteria etc. should clearly mentioned where relevant . • Subject exclusion criteria , including are exhaustive statement on criteria for pre admission exclusions. 11/18
- 12. •Subject withdrawal criteria and procedures specifying – when & how to withdraw subjects from the treatment , type & timing of data to be collected from withdrawn subjects , whether & how subjects are to be replaced and follow up on withdrawn subjects •Statistical justification for the number of subjects to be included in the study. 6). Handling of Products •Measures to be implemented to ensure the safe handling and storage of the pharmaceutical products •System to be followed for labelling of the product •The label should necessarily contain the following information : the words “ For Clinical Studies only “ , name or code of the study , name & contact number of Investigator , name of institution , Subjects identification code . 12/18
- 13. 7) Assessments of Efficacy •Specification of the effect parameters to be used •Description of how effects are measured and recorded •Time & periodicity of effect recording •Description of special analyses / test to be carried out 8) Assessment of Safety •Specification of safety parameters •Methods & periodicity for assessing & recording safety parameters •Procedures for eliciting reports of and for recording and reporting ADR / adverse events & inter current illnesses •Type & duration of the follow up of subjects after adverse events •Information on establishment of the study code ,where it will be kept and when , how & by whom it can be broken in the event of an emergency. 13/18
- 14. 9) Statistics •Description of statistical methods to be employed •Number of study subjects needed to achieve the study objective , and statistical consideration on which proposed number of subjects is based. •Procedures for managing missing data ,unused data & unauthentic data . •Procedures for reporting any deviation from original staitsitcal plan should be stated & justified in protocol •Selection of subjects to be included in final analyses (eg. All randomized subjects/all dosed subjects/all eligible subjects/evaluable subjects. 14/18
- 15. 10.Data handling and Management A statement should be clearly made in the protocol that “That the investigator(s)/institution(s) will permit study related monitoring ,audits ,ethics committee review and regulatory inspection(s) providing direct access to source data / documents. •Procedures for handling & processing records of effects and adverse effects to the product(s) under the study. •Procedures for keeping of patients records for each individual taking part in the study .Records should facilitate easy identification of the individual subjects . 15/18
- 16. 11. Quality Control & Quality Assurance •A meticulous and specified plan for the various steps & procedures for the purpose of controlling & monitoring the study effectively. •Specifications & instruction for anticipated deviations from protocol. •Allocation of duties & responsibilities with research team and their co-ordination. •Instructions to staff including study description (the way study is to be conducted & procedures for drug administration) . •Address & contact number etc. Enabling any staff member to contact the research team any hour . •Considerations of confidentiality problems ,if any rise. •Quality control of methods and evaluations procedures 16/18
- 17. 12.Finance and Insurance •All financial aspects of conducting and reporting a study arranged and a budget made out. •Information should be available about the sources of economic support (eg. Foundation , private or public funds, sponsor/manufacturer) . Likewise it should be stated how the expenditure should be distributed eg. Payment to subjects ,refunding expenses of subjects , payment for special tests , technical assistance, purchase of apparatus ,payment of investigator. •Study subjects should be satisfactorily insured against any injury caused by the study . •The liability involved parties must be clearly agreed & stated before the start of study 17/18
- 18. 13. Publication Policy •A publication policy, if not addressed in a separate agreement, should be described in the protocol . 14. Evaluation •A specified account for how the response to be evaluated . •Methods of computation & calculation of effects •Descriptions of how to deal with report subjects withdrawn / dropped out of the study 15. Supplements & appendices The following documents should be appended with the protocol •Information to study subjects and mode of providing it. •Instructions to staff •Descriptions of special procedures . 18/18
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