Clinical trail protocol and development

Contents of clinical trial protocol

1. clinical trail protocol and development Presented by; BALADATTA SAI.CHINTAM 1 7 A B 1 R 1 9 V I G N A N P H A RMACY C O L L EGE G U N T U R , A N D H RAPRADESH

2. CLINICAL TRAILS As per ICMR, A clinical trail is any research/study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects in health outcomes. The intervention could be drugs, vaccines, biologics, phytopharmaceuticals , radiopharmaceuticals, diagnostic agents, medical devices, surgical techniques etc….. Clinical trails are usually well controlled studies. At present, Due to huge patient load, wide variety of diseases, low operational cost, sufficient infrastructure India is a hub for clinical trails.

3. CLINICAL TRAIL PROTOCOL DRUGS AND COSMETICS ACT (schedule Y): Requirements and guidelines for permission to import and / manufacture of new drugs for sale or to undertake clinical trails. ICH GUIDELINES-E6(R2): Good clinical practice addendum to ICH, clinical trail protocol and protocol amendments. INDIAN COUNCIL OF MEDICAL RESEARCH: National ethical guidelines for biomedical and health research involving human participants, these deals with the ethical consideration.

4. CLINICAL TRAIL REGISTRY-INDIA

5. CLINICAL TRAILS REGISTRY-INDIA

6. protocols? To clarify the research question. To compile existing knowledge. To formulate a hypothesis and objectives. To clarify ethical considerations. To decide about a study design. To apply for funding. To have a guideline and tool for the research team.

7. PROTOCOL WRITING It is acomplete written description and scientific rationale for a research activity involving human subjects. a)Objectives. b)Design. c)Methodolgy. The PI must know the answers for; # Is it reasonable? Do we have the resources? # What are the significant risks? # Do e have the patient population? Should be able to write whole CT in few lines.

8. WHO READS PROTOCOLS ? The written protocol language / content should be understood by: Other physicians Nurses CRAs (Clinical Research Associates) Scientific reviewers Board members Press and Journals IC (Informed Consent) for a lay person

9. parts of the protocol Title page. Signature page. Content page. List of abbrevations. Introduction/Abstract. Objectives. Background/Rationale. Eligibilty Criteria. Study design/Methods. Safety/Adverse events. Regulatory Guidence. Statistical section. Human subjects protection.

10. 1) title page Title page intoduce the document, its title, precise, number, sponsor and author to the reader. Protocol identifying number and date. Full title page should include summary, study design, medicinal products, nature of treatment, patient population setting indication (in-patient, out-patient), randomised double multiple studies. Name and address of sponsor and monitor. Sponsor names and list of responsibilities ith agreed allocations. Name and address of the person authorised to sign the protocol. Generally, chief investigator for multicentric trial or principle investigator for single centre trails. Name and address of the clinical laboratory and other institutions involved in the trail.

11. 2) signature page Signature page should include signatures of all health care professionals and others, who participated in the clinical trial. Signature page should also include contact details of participating site, sponsor and sponsor medical advisor. signature of sponsor responsible persons not named on the cover page.

12. 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. In contet page, Table of in-text tables, Table of in-text figures should be separetly written. Table of in-text tables contains schedule of assessments, instruction of trail periods,sampling collection schedule, heamotology assessments, bilogical assessments, estimated blood sample volumes per subject. Table of in-text figures contains schematic chart of trial design.

13. 4) list of abbrevations All abbrevations should be listed and defined. Accepted international medical abbrevations should be standardised within each project. EXAMPLES: DBP (Diastolic Blood Pressure) CRU (clinical Research Unit) ICF (Informed Consent Form) SBP (Systolic Blood Pressure) MDRD (Modification of Diet in Renal Disease) SEM (Standard Error of the Mean)

14. 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. Introduction/Abstarct shoul be; PRECISE (strictly conforming to a pattern, standard) CONCISE (giving a lot of information clearly and in a few words) SPECIFIC (descriptive should be noted round the point)

15. 6) objectives Objective should be stated clearly as hypothesis to be tested. Each objective should have a corresponding discussion in the statistical section. A) PRIMARY OBJECTIVES: The primary research objective should be an abridged (shortened) form of the problem statement. B) SECONDARY OBJECTIVES: The secondary objectives should try to establish a relationship beteen the different variables of a research topic and suggest possible recommendations for dealing with the main research problems.

16. 7) background & 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. Double check all citations. common mistakes: Name misspellings (including rong initials) Wrong journal names Wrong years of publication Wrong volume numbers

17. 8) elgibilty criteria Inclusion and Exclusion criteria are the conditions that must be met in order to participate in a clinical trial. A) INCLUSION CRITERIA: Inclusion criteria contain only those items that define the target population desired for study, within the limits of known safety coverage, should generally allow inclusion of the broadest representation of the population for intended use, but usually not beyond. B) EXCLUSION CRITERIA: Exclusion criteria are defined as features of the potential study participants who meet the inclusion criteria but present with additional characteristics that could interfere with the success of the study or increase their risk for an unfavorable outcome.

18. wRITING ELIGIBILTY CRITERIA FOR PATIENT Eligibilty criteria are the largest barrier to clinical trails. There is no guideline for writing these criteria. Poorly written or poorly conceived criteria may affect the scientific validity of CT. THE POINTS TO BE CONSIDERED TO WRITE A GOOD ELIGIBILITY CRITERIA: The number of eligibilty criteria should be kept to a minimum. Criteria should include only those absolutely necessary to ensure scientific validity and patient safety. Eligibilty criteria should be clearly defined and verifiable by an external auditor. Eligibility criteria should be straightforward and unambigous (precise).

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 foe the participating size. Parts of the study design section may include: Initial evaluations. Screening tests. Required lab tests. Details of treatment. Device specifications. Dose scheduling and monitorng

20. 10) safety Adverse effect and sid effect are terms commonly associated ith drugs. They are used by nurses and doctors, to refer to undesirable effects of a medication on a patient. The safety section or adverse events section should include; Detailed information for reportin adverse events, including reporting to the FDA and the sponsor. If applicable, Unblinding process (code-breaking). Lists of expected adverse events.

21. 11) the statistical section The study objectives and study design elements in the statisitical section should be described in the objectives section. The descriptions and defintions of toxicities in the statistical section match this in the safety or adverse event section. Elements included in the statistical section; Efficasy analyses. Safety analyses. Missing value handling and subject evaluability. Statistical adjustments for multiple endpoints.

22. 12) human-subjects protection A protocol ithout the human-subject protections section ill not be accpted for review by the IRB (Institutional Review Board). This sction includes discussion of: Subject selection and exclusion. Proposed methods of patient recruitment. Recruitment or exclusion of spcila subjects, including vulnerable subjects. Lists of potential risks and benefits, including justification for risks.

23. informed consent Informed consent process ensures the individuals autonomy, to voluntarily participate in a trail. 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 and information. statement of voluntary participation.