Title 13. DESIGNING OF CLINICAL STUDY DOCUMENTS (Protocol, CRF, ICF).pdf ✅

PHARMD GURU Page 1 PROTOCOL The protocol is a document that describes how a clinical trial will be conducted and ensures the safety of the trial subjects and the integrity of the data collected. It describes the background, rationale, objectives, design, methodology, statistical considerations, and organization of a clinical research project. A well-designed study relies predominantly on a thoroughly considered, well-structured and complete protocol. Relevant components of Protocol: ➢ General information: 1. Protocol title, protocol identifying number and date. 2. Name, address & contact numbers of the sponsor and the monitor / CRO. 3. Name and title of the persons authorized to sign the protocol and the protocol amendments for the sponsor. 4. Name, title, address and contact numbers of the sponsor's medical expert for the study. 5. Name, title, address and contact numbers of the investigator who is/are responsible for conducting the study, along with their consent letter. 6. Name, address and contact numbers of the institution - clinical laboratories and / or other medical and technical departments along with the particulars of the head of the institution and the relevant department. ➢ Objectives and Justification: 1. Aims and objectives of the study. 2. Name and description of the investigational products. 3. Summary of the known and potential risks and benefits, if any, to human subjects. 13. DESIGNING OF CLINICAL STUDY DOCUMENTS (Protocol, CRF, ICF)
PHARMD GURU Page 2 4. Description of and justification for the ROA, dosage regimen and treatment periods for the pharmaceutical product being studied and the product being used as control. 5. A statement that the study will be conducted in compliance with the protocol, GCP and the applicable regulatory requirements. 6. Description of the inclusion & exclusion criteria of the study population 7. References to the literature and data that are relevant to the study and that provide background for the study. ➢ Ethical Considerations: 1. General ethical considerations related to the study. 2. Description of how patients or healthy volunteers will be informed and how their consent will be obtained. 3. Possible reasons for not seeking informed consent. ➢ Study design: The scientific integrity of the study and the credibility of the data from the study depend upon the study design. It includes: 1. Description of the type of the study (randomized, comparative, blinded, open, placebo-controlled), study design (parallel groups, cross-over technique), blinding technique (double or single-blind), randomization (method and procedure). 2. A schematic diagram of the study design, procedures, and stages. 3. Medications/treatments permitted (including rescue medications) and not permitted before and / or during the study. 4. A description of the study treatments, dosage regimen, route of administration and the dosage form of the investigational product and the control proposed during the study. 5. A description of the manner of packaging and labeling of the investigational product. 6. Duration of the subject participation and a description of the sequence of all study periods including follow-up, if any.
PHARMD GURU Page 3 7. Proposed date of initiation of the study. 8. Justification of the time-schedules. E.g. How far the safety of the active ingredients, medicinal products has been tested, the time course of the disease in question. 9. Discontinuation criteria for study subjects and instructions on terminating or suspending the whole study or a part of the study. ➢ Inclusion, Exclusion, and Withdrawal of Subjects: 1. Subject inclusion criteria: specifications of the subjects (patients / healthy volunteers) including age, gender, ethnic groups, prognostic factors, diagnostic admission criteria, etc. should be clearly mentioned where relevant. 2. Subject exclusion criteria, including an exhaustive statement on criteria for preadmission exclusions. 3. Subject withdrawal criteria (i.e. terminating investigational product treatment/study treatment) and procedures specifying – when and how to withdraw subjects from the treatment, type, and timing of the data to be collected from withdrawn subjects, whether and how subjects are to be replaced and the follow-up on the withdrawn subjects. 4. Statistical justification for the number of Subjects to be included in the Study. ➢ Handling of the Products: 1. Measures to be implemented to ensure the safe handling and storage of the pharmaceutical products. 2. System to be followed for labeling of the products (code numbering etc.) 3. The label should necessarily contain the following information: the words - “For Clinical Studies only”, the name or a code number of the study, name and contact numbers of the investigator, name of the institution, subject’s identification code. ➢ Assessment of Efficacy: 1. Specifications of the effect parameters to be used. 2. Description of how effects are measured and recorded. 3. Time and periodicity of effect recording.
PHARMD GURU Page 4 4. Description of special analyses and/tests to be carried out (pharmacokinetics, clinical, laboratory, radiological, etc). ➢ Assessment of Safety: 1. Specifications of safety parameters. 2. Methods and periodicity for assessing and recording safety parameters. 3. Procedures for recording and reporting adverse drug reactions and / or adverse events and inter-current illnesses. 4. Type and duration of the follow-up of the subjects after adverse events. 5. Information on the establishment of the study-code, where it will be kept and when, how and by whom it can be broken in the event of an emergency. ➢ Statistics: 1. Description of the statistical methods to be employed, including the timing of any planned interim analysis. 2. A number of study subjects needed to achieve the study objective and other statistical considerations. 3. Detailed break-up of the number of subjects planned to be enrolled at each study site (in case of multi-center studies) 4. Procedures for managing missing data, unused data and unauthentic data 5. Procedures for reporting any deviations from the original statistical plan. 6. Selection of the subjects to be included in the final analyses (e.g. all randomized subjects / all dosed subjects / all eligible subjects / evaluable subjects). ➢ Data handling and management: A statement should be clearly made in the protocol that the investigator/institution will permit study-related monitoring, audits, ethics committee review and regulatory inspections providing direct access to source data/documents. A copy of the CRF should be included in the protocol. Besides, the following details should be given:
PHARMD GURU Page 5 1. Procedures for handling and processing records of effects and adverse events to the product under study. 2. Procedures for the keeping of patient lists and patient records for each individual taking part in the study. 3. Records should facilitate easy identification of the individual subjects. ➢ Quality control and quality assurance: 1. A meticulous and specified plan for the various steps and procedures for the purpose of controlling and monitoring the study most effectively. 2. Specifications and instructions for anticipated deviations from the protocol. 3. Allocation of duties and responsibilities within the research team and their coordination. 4. Instructions to staff including study description (the way the study is to be conducted and the procedures for drug usage and administration). 5. Addresses and contact numbers etc. enabling any staff member to contact the research team at any hour. 6. Considerations of confidentiality problems, if any arise. 7. Quality control of methods and evaluation procedures. ➢ Finance and insurance: 1. All financial aspects of conducting and reporting a study may be arranged and a budget made out. 2. Information should be available about the sources of economic support (e.g. foundations, private or public funds, sponsor/manufacturer). 3. Likewise, it should be stated how the expenditures should be distributed e.g. payment to subjects, refunding expenses of the subjects, payments for special tests, technical assistance, purchase of apparatus. 4. Study Subjects should be satisfactorily insured against any injury caused by the study. ➢ Publication policy: 1. A publication policy, if not addressed in a separate agreement, should be described in the protocol.