Single core = a single report which contains most important information of the study.
Ambiguity = when sth. has more than one possible meaning and may therefore cause confusion. , Demographic = a study based on statistics of births, deaths and disease.
Apparent = readily visible or obvious.
Synopsis= a short description of content. , p-value= value in probability . , Synopsis = summary or outline.
Parentheses= a remark which is added to sentence, often to provide explanation or extra information.
Declaration of Helsinki = well-being of the human subject should take precedence over the interests of science and society.
Concomitant = occurring together
Demographic = A study based on statistics of births, deaths and disease. Baseline characteristics = common characters.
By-Patients Displays = While individual patient data ordinarily can be displayed in tabular listings, it has on occasion been helpful to construct individual patient profiles in other formats, such as graphic displays .
Ich efficacy3 by Ramkrisna Bhunjawa
By : Ramkrisna
Basic Structure Of the Guideline Introduction to the Guideline……. The objective of this guideline is to allow the compilation of a single core clinical study report acceptable to all regulatory authorities of the ICH regions.This guideline is mainly aimed at efficacy and safety trials, the basic principles and structure described can be applied to other kinds of trials, such as clinical pharmacology studies.
Cont………….According to the guideline study report should be "integrated’’ means full report of an individual study of any therapeutic, prophylactic or diagnostic agent conducted in patients, in which the clinical and statistical description, presentations, and analyses are integrated into a single report, incorporating tables and figures into the main text of the report or at the end of the text, with appendices containing the protocol, sample case report forms, investigator related information, information related to the test drugs/IP including active control/comparators,
Contd………. , technical statistical documentation, related publications, patient data listings, and technical statistical details such as derivations, computations, analyses, and computer output etc. The guideline is intended to assist sponsors in the development of a report that is complete, free from ambiguity, well organised and easy to review. The report should describe demographic and other potentially predictive characteristics of the study population . In the case of very large trials, some of the provisions of this guideline may be impractical or inappropriate.
There are sixteen sections which describeprecisely about structure and contents of clinical study reports. • Given below…….• 1. Title Page.• 2. Synopsis.• 3. Table of Contents for the Individual Clinical Study Reports.• 4. List of abbreviations and Definition of the Term.• 5. Ethics.
• 6. Investigators and Study Administrative Structure.• 7. Introduction.• 8. Study Objectives.• 9. into 8 sub sec.) Investigational Plan(it is divided• 10. Study Patients.• 11. Efficacy Evaluation.• 12. Safety Evaluation.• 13. Discussion and Overall Conclusions.• 14. Tables, Figures and Graphs Referred to but not Included in the Text• 15. Reference List.• 16. Appendices.
1. Title Page. Study Title. Name of the test drug/I.P. Indication Studied. Title should be in apparent. If it is not a brief details in 1 or 2 lines should be there about design, comparison, duration, dose and study population. Name of the Sponsor. Protocol Identification. Development phase of study. Study initiation date. Date of early study termination (if any). Date of completion of study.
Name, Telephone no. and Fax no. of Sponsor or a responsible person. Statement for complied with GCP including archiving Essential Documents. Date of Report. Name and affiliation of PI or co-Investigator. 2. SynopsisThe brief synopsis (usually 3 pages) that summarize studyshould include numerical data illustrated to result not justtext and p-values.
3. Table of Contents for Individual Clinical Study Report. The table of contents should include: the page number or other locating information of each section, including summary tables, figures and graphs; a list and the locations of appendices, tabulations and any case report forms provided.
4. List of Abbreviation and Definition of Terms A list of the abbreviations, and definitions of specialised or unusual terms or measurements units used in the report should be provided. Abbreviated terms should be spelled out and the abbreviation indicated in parentheses at first appearance in the text.
5. Ethics It is described in 3 sub section…… i. IEC/IRB.ii. Ethical Conduct of the study.iii. Patient information and Consent.(i) IEC/IRB : It should be confirmed that the study and any amendments were reviewed by an IEC/IRB. A list of all IECs or IRBs consulted should be given, ifrequired by the regulatory authority, the name of thecommittee Chair person should be provided.
(ii) Ethical Conduct of the study :It should be confirmed that the study was conducted in accordance with the ethical principles that have their origins in theDeclaration of Helsinki.(iii) Patient Information and Conduct : How and when informed consent was obtained in relation topatient enrolment, (e.g., at allocation, pre-screening) should bedescribed.Representative written information for the patient (if any) and asample patient consent form should be provided.
6. Investigators and Study Administrative Structure. The administrative structure of the study (e.g., PI, co- investigator, steering committee, administration, monitoring and evaluation committees, institutions, statistician, central laboratory facilities, C.R.O., clinical trial supply management) should be described briefly in the body of the report.(appendix 16.1.4) The list should include…. (a) Investigators. (b) Any other person carrying out observations of primary or other major efficacy variables, such as a nurse, physicians assistant, clinical psychologist, clinical pharmacist, or house staff physician.
(c) The author(s) of the report, including the responsible biostatistician(s). 7. Introduction The introduction should contain a brief statement (max: 1 page) placing the study in the context of the development of the test drug/IP, relating the critical features of the study (e.g., rationale and aims, target population, treatment, duration, primary endpoints) to that development. Any guidelines that were followed in the development of the protocol or any other agreements/meetings between the sponsor/company and regulatory authorities that are relevant to the particular study, should be identified or described.
8. Study Objective A statement describing the overall purpose(s) of the study should be provided. 9. Investigational Plan It is described in 8 sub sections…. (i) Overall study design and plan description. (ii) Discussion of study design, including the choice of control group. (iii) Selection of study population. (iv) Treatments. (v) Efficacy and Safety variables.
(vi) Data Quality Assurance. (vii) Statistical methods planned in protocol and determination of sample size. (viii) Changes in the conduct of the study or planned analysis. (i) Overall study design and plan description : The overall study plan and design (configuration) of the study (e.g., parallel, cross-over) should be described briefly but clearly, using charts and diagrams as needed. If any information used in this section comes source other than protocol should include…. Treatment studied, patient population and number of patients included, level and method of blinding/ masking, kind of study control, sequence and duration of all study period.
(ii) Discussion of study design, including the choice of control group : Generally, the control (comparison) groups that are recognised are placebo concurrent control, no treatment concurrent control, active treatment concurrent control, dose comparison concurrent control, and historical control. In addition to the type of control, other critical design features that may need discussion are use of a cross-over design and selection of patients with particular prior history, such as response or non-response to a specific drug or member of a drug class. Other specific features of the design may also deserve discussion, including presence or absence of washout periods and the duration of the treatment period, especially for a chronic illness.
(iii). Selection of study population : This sub section described in 3 co-sections…… Inclusion Criteria. Exclusion Criteria. Removal of Patients from therapy or assessment. Inclusion Criteria : The patient population and the selectioncriteria used to enter the patients into the study, suitability of thepopulation for the purposes of the study should be described.Screening criteria and any additional criteria for randomisation orentry into the test drug/IP treatment part of the trial should bedescribed. If there is reason to believe that there were additionalentry criteria, not defined in the protocol, the implications of theseshould be discussed.
Contd….For example, some investigators may have excluded, or entered into other studies, patients who were particularly ill or who hadparticular baseline characteristics.Exclusion Criteria : The criteria for exclusion at entry into thestudy should be specified and the rationale (e.g., safety concerns,administrative reasons or lack of suitability for the trial) provided.The impact of exclusions on the study should be discussed insection 13 of the study report, or in an overview of safety andefficacy.
Removal of Patients from therapy or assessment. Thepredetermined reasons for removing patients from therapy orassessment observation(if any), as should the nature and duration of any planned follow-up observations in those patients should bedescribed. (iv) Treatments : It described in 8 co-sections….. Treatments Administered. Identity of Investigational Product(s). Method of Assigning Patients to Treatment Groups. Selection of Doses in the Study. Selection and Timing of Dose for each Patient. Blinding.
Prior and Concomitant Therapy. Treatment Compliance. (v) Efficacy and Safety variables : It divided in 4 co-section…… Efficacy and Safety Measurements Assessed and Flow Chart. (Annex iii). Appropriateness of Measurements . Primary Efficacy Variable(s) . Drug Concentration Measurements .
(vi) Data Quality Assurance : The quality assurance and quality control systemsimplemented to assure the quality of the data should be described in brief. If none were used, this should be stated. (vii) Statistical methods planned in protocol and determination of sample size : It is described in 2 co-sections……. Statistical and Analytical Plans :In this section emphasis should be on which analyses,comparisons and statistical tests were planned, not on whichones were actually used. Planned monitoring of the results of the study should bedescribed.
Determination of Sample Size :The planned sample size and the basis for it, such as statisticalconsiderations or practical limitations, should be provided. Methods for sample size calculation should be given together withtheir derivations or source of reference. (viii) Changes in the conduct of the study or planned analysis : Any change in the conduct of the study or planned analyses (e.g., dropping a treatment group, changing the entry criteria or drug dosages, adjusting the sample size etc.) instituted after the start of the study with reason, procedure and responsible person or group should be described.
10. STUDY PATIENTS It is described in 2 sub-section……. the study, using figures or DISPOSITION OF PATIENTS : There should be a clear accounting of all patients who entered tables in the text of the report. There should also be a listing of all patients discontinued fromthe study after enrolment, as it is given in appendix 16.2 . PROTOCOL DEVIATIONS : All important deviations related to study inclusion or exclusion criteria, conduct of the trial, patient management or patient assessment should be described .
11. EFFICACY EVALUATION It is described in 4 sub-section….. DATA SETS ANALYSED : Exactly which patients were included in each efficacy analysis should be precisely defined. . DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS : Group data for the critical demographic and baseline characteristics of the patients, as well as other factors arising during the study that could affect response, should be presented in this section and comparability of the treatment groups for all relevant characteristics should be displayed by use of tables or graphs in section 14.1.
Measurement of Treatment Compliance : Eg. drug concentrations in body fluids should be summarised,analysed by treatment group and time interval of Individual Patients Efficacy Results and Tabulation Data : It is divided into 7 co-section… Analysis of Efficacy. Statistical/Analytical Issues. Tabulation of Individual Response Data. Drug Dose, Drug Concentration, and Relationships to Response. Drug-Drug and Drug-Disease Interactions. By-Patient Displays.
Efficacy Conclusions. 12. SAFETY EVALUATION This section described in 6 sub-section…. Extent of Exposure. Adverse Events. Deaths, Other Serious Adverse Event, and Other Significant Adverse Events. Clinical Laboratory Evaluations. Vital Sign, Physical Findings and Other Observation Related to Safety. Safety Conclusions.
13. DISCUSSION AND OVERALL CONCLUSIONSThe efficacy and safety results of the study and the relationship of risks and benefit should be briefly summarised and discussed,referring to the tables, figures, and sections above as needed. Thepresentation should not simply repeat the description of results orintroduce new results. 14. TABLES, FIGURES AND GRAPHS REFERRED TO BUT NOT INCLUDED IN THE TEXTFigures should be used to visually summarise the importantresults, or to clarify results that are not easily understood fromtables.
Section 14 is described in 3 sub-sec…….. DEMOGRAPHIC DATA Summary figures and tables. EFFICACY DATA Summary figures and tables. SAFETY DATA Summary figures and tables. 15. REFERENCE LIST A list of articles from the literature pertinent to the evaluation of the study should be provided.
Contd…..References should be given in accordance with the internationallyaccepted standards of the 1979 Vancouver Declaration on "Uniform Requirements for Manuscripts Submitted to BiomedicalJournals" or the system used in "Chemical Abstracts". 16. APPENDICES This section should be prefaced by a full list of all appendices available for the study report. Where permitted by the regulatory authority, some of the following appendices need not be submitted with the report but need to be provided only on request. Such as…..
Study Information. Patients Data Listings. Case Report Form. Individual Patient Data Listings (US archival listings).