Gcp guidelines

Guidelines for clinical trials

1. GCP Guidelines Dr. Nilesh Siddhawar, JR1, Dept. of Pharmacology, VNGMC, Yavatmal

2. Contents- Introduction Historical Background Principles of Guidelines Ethics Committee Informed Consent Process Responsibilities of Sponsor, Monitor & Investigator Guidelines For Special Concern Conclusion

3. Good Clinical Practice is a set of guidelines which encompasses the design, conduct, termination, audit, analysis, reporting and documentation of the studies involving human subjects

4. Historical Background Nuremberg Code, 1946 Kefauver Amendments, 1962 Declaration of Helsinki, 1964 Belmont Report, 1979

5. Nuremberg Code(1946) German Physicians conducted medical experiments on prisoners of war without their consent . Most of the participants of these experiments died or were permanently crippled.

6. In December 9, 1946 - American military tribunal opened criminal proceedings against 23 leading German physicians The Nuremberg Code was established in 1948, stating that " The voluntary consent of the human participant is absolutely essential," Nuremberg Code was the first international document which advocated voluntary participation and informed consent .

7. Kefauver Amendments(1960) 6000-12000 children had congenital anomalies d/t maternal use of Thalidomide. 1962 US Senate hearings Kefauver Amendments passed into law - For the first time, drug manufacturers were required to prove to the FDA the effectiveness of their products before marketing them

8. Declaration Of Helsinki Adopted by the 18th WMA general assembly Helsinki, Finland, June 1964. It has since undergone seven revisions (the most recent at the general assembly in October 2013) . A statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects. The Declaration specifically addressed clinical research, reflecting changes in medical practice from the term 'Human Experimentation ' used in the Nuremberg Code

9. The US Public Health Services conducted a Syphilis Study on 600 low income African-American individuals Stopped in 1972 led to the 1979 Belmont Report and the establishment of OHRP. Tuskegee Syphilis Study- 1932 to 1972

10. A comprehensive representation of the development of GCP can be found in a literature review of …..

11. The Principles Of GCP Follow ethical principles according to Declaration of Helsinki Essentiality Voluntariness, informed consent and community agreement Non-exploitation Privacy and confidentiality Precaution and risk minimisation Professional competence

12. 8. Accountability and transparency 9. The maximisation of the public interest and of distributive justice 10. Institutional arrangements 11. Public domain 12. Totality of responsibility 13. Compliance

13. Ethics Committee Responsibilities To protect the dignity, rights and well being of research participants. To ensure that universal ethical values and international scientific standards are followed . To assist in the development and the education of a research community responsive to local health care requirements

14.   Composition 1.      Chairperson 2.      1-2 basic medical scientists (preferably one pharmacologists). 3.      1-2 clinicians from various Institutes 4.      One legal expert or retired judge 5.      One social scientist / representative of non-governmental voluntary agency 6.      One philosopher / ethicist 7.      One lay person from the community 8.      Member Secretary

15. The researcher should submit an appropriate application to the IEC along with the study protocol. The IEC should be able to provide complete and adequate review of the research proposals submitted to them. All documentation and communication of an IEC are to be dated, filed and preserved according to written procedures. Strict confidentiality is to be maintained.

16. Informed Consent Process The expected duration participation The benefits as an outcome of research Any alternative procedures or courses of treatment that might be as advantageous to the subject as the procedure or treatment to which she/he is being subjected; Any foreseeable risk or discomfort to the resulting from participation in the study. Right to prevent use of his/her biological sample (DNA, cell-line, etc.)

17. Confidentiality of records Free treatment for research related injury . Compensation of subjects for disability or death resulting from such injury. Freedom of individual to participate and to withdraw from research any time without penalty or loss of benefits. The identity of the research teams and contact persons with address and phone numbers.  

18. Compensation for Participation Subjects may be paid for the inconvenience and time present, and should be reimbursed for expenses incurred. Payments should not be large or the medical services extensive. All payments should be approved by the IEC. When a subject is withdrawn from research for medical reasons related to the study the subject should get the benefit for full participation

19. Selection of Special Groups As Research Subject Pregnant or nursing women : Trials that are designed to protect or advance the health of pregnant or nursing women or foetuses. The justification of participation would benefit subject from investigations, drugs, vaccines or other agents that promise therapeutic or preventive benefits. Research related to termination of pregnancy. Research related to pre-natal diagnostic techniques

20. Children- The study in children should always be carried out after the phase III clinical trials in adults. Research should be conducted in settings in which the child and parent can obtain adequate medical and psychological support. The child's refusal to participate in research must always be respected unless there is no medically acceptable alternative to the therapy provided The assent of the child should be obtained to the extent of the child's capabilities.

21. Responsibilities Of Sponsor Selection the investigator / institutions. The sponsor should establish detailed standard operating procedures (sop’s). Allocation of duties and responsibilities. Make arrangements for safe and secure custody of all study related documents and material. Compensation for participation. Confirmation of review by the ethics committee .

22. Sponsor is responsible for providing the Investigator with an Investigator’s Brochure. 8. Supply, storage and handling of Pharmaceutical Products. The Sponsor should expedite the reporting to all concerned of all serious or unexpected adverse drug reactions. 10. Sponsor should perform an audit as a part of QA system In case of foreign sponsor it shall appoint a local representative or CRO to fulfil the appropriate local responsibilities.

23. The Monitor: The monitor should have adequate medical, pharmaceutical and / or scientific qualifications and clinical trial experience. He is a principal communication link between the sponsor and the investigator and is appointed by the sponsor. 

24. Responsibilities Verification of investigator(s) qualifications, expertise and the resources to carry out the study. Verification of institutional facilities like laboratories, equipment, staff, storage space etc.  Assessments of the protocol compliance and data handling .  He should assist the investigator in reporting the data and results of the study to the sponsor.

25.    Investigator  Should have qualifications prescribed by MCI. Should be thoroughly familiar with the safety, efficacy and appropriate use of the investigational product .  Responsible for all study related medical decisions.   Investigator has the primary responsibility for investigational products accountability at the study site.  Responsible for ensuring the unbiased selection of an adequate number of suitable subjects 

26. Record keeping and data handling All steps involved in data management should be documented . For electronic data processing only authorised person should be allowed to enter or modify the data in the computer. If trial data are entered directly into the computer to ensure validation there must be a signed and dated printout and backup records. The sponsor ensure electronic data processing system verified for completeness, accuracy, reliability and validation.

27. Quality Assurance The Sponsor is responsible quality assurance that the Study is performed and the data is generated, recorded and reported in compliance with the Protocol, GCP. Documented Standard Operating Procedures are a prerequisite for quality assurance .

28. SPECIAL CONCERNS 1. Guidelines for vaccine trials- Conducted by trained investigator in institute with facility of laboratory evaluation for seroconversion. Active or live-attenuated vaccine > risk of producing infection. The subjects should be informed. For all the recombinant vaccines/products - guidelines issued by the Dept. of Biotechnology should be strictly followed.

29. 2. Guidelines for Clinical Trials of Contraceptives When implant is used for contraception, follow up for removal of the implant should be done. Children born due to failure of contraceptives under study should be followed up for any abnormalities .

30. Guidelines for Clinical trials with surgical procedures/ medical devices Safety data of the medical device in animals should be obtained. Phase I of drug trial is not necessary for trial on devices Patient information sheet should contain information about procedures to be adopted if the patient decides to withdraw from the trial.

31. Guidelines for Clinical trials for Diagnostic Agents - Use of Radio-active Materials and X- Rays Research should be performed on patients undergoing the procedures for diagnostic or therapeutic purposes. Safety measures should be taken to protect research subjects The protocol should make provisions for detecting pregnancies Non-radioactive diagnostic agents are considered as drugs and the same guidelines should be followed

32. Guidelines for Clinical trials of Herbal Remedies and Medicinal Plants Same guidelines applied for herbal medicines as well. Herbal remedies currently in use or mentioned in traditional system of medicine- No neccessity to undertake phase I studies Such clinical trials be carried out only when a competent Ayurvedic, Siddha or Unani physician is a co-investigator

33. Conclusion GCP Guidelines safeguard the rights and safety of trial subjects It also guides clinicians for proper conduction of research. It ensures accuracy, legibility and acceptability of outcome of research. GCP is amalgamation of science and practical wisdom gained by personal experiences.