Institutional review board/Independent ethics Committee

From history and with case studies

1. institutional review board (IRB) (or) independent ethics committe (IEC) Presented b y , B A L A D A T T A S A I . C H I N T A M 1 7 A B 1 R 1 9 V I G N A N P H A RMACY C O L L E G E G U N T U R , A N D H R APRADESH .

2. introduction Experimentation on human being is subject to ethical standards that promote respect for all and protect their health and rights. The “Institutional Review Board” (IRB) is a local administrative body established to protect the rights, safety and well-being of human research subjects recruited to participate in a clinical research. The IRB has the authority to approve, require modification in, or disapprove all research activities that fall within its jurisdiction. The IRB provides assurances to research subjects that every reasonable attempt has been made to protect their rights and safety as subjects.

3. why do we need irb? The IRB is in place to uphold the three principles of the Belmont report : PRINCIPLE 1: Respect for persons. voluntary participation. Privacy and confidentiality protected. PRINCIPLE 2: Beneficence Risks are minimized. Conflicts of interest managed adequately. PRINCIPLE 3: Justice Vulnerable subjects not targeted because of convenience. People likely to benefit from research are not systematically excluded.

4. history Formal review procedures for institutional human subjects studies wre orginally developed in direct reponse to research abuses in the 20th century. Among the most notorious of these abuses were the experiments of nazi physcians during world war-II.

5. history The Tuskegee syphilis study , a long term project conducted between 1932 to 1972 by the U.S. public health service.

6. Numerous human radiation experiments conducted during the cold war, one of them is Stanford prison experiment. Project MKULTRA is a code given to the experiments conducted by CIA.

7. declaration of helsinki The result of these abuses was the National Research Act of 1974 has developed the Declaration of helsinki as a statement of ethical priciples to provide guidance to physcians and other participants in medical research involving human subjects. PRINCIPLES: It is the duty of the phyiscian in medical research to protect the life, health, privacy and dignity of the human subject. Medical research involving human subjects must conform to generally accepted scientific principles.

8. declaration of helsinki The design and performance of each experimental procedure involving human subjects should be clearly formulated in an experimental protocol. Independent committee should be in conformity with the laws and regulations of the country in which the research experiment is performed. the committee has the right to monitor ongoing trials. Medical research involving human subjects should be conducted only by scientifically qualified persons under the supervision of a clinically competent medical person. Physcians should cease any investigation if the risks are found to outweigh the potential benefits or if there is conclusive proof of positive and benificial results.

9. constitution of irb The IRB should consist at least seven members , who collectively have the qualifications and experience to review and evaluate the science, medical aspects, and ethics of the proposed trial. Viz ; Chairperson-Appointed (from outside the institution) 1-2 basic medical scientists 1-2 clinicians from various institutes One legal expert or retired judge One social scientist One philosopher or ethicist Secretary member

10. quorum of irb For reviewing and making decision on each protocol the quorum of IRB should be atleast five members with the following representations; Basic medical scientists (preferably one pharmacologist) Clinicians Legal expert Social scientist/Representative of non-governmental voluntary agency/philosopher/ethicist/theologian Lay person from the community Further, based on the requirement of research area (AIDS, genetic disorders etc…) specific patient groups may also be represented in the IRB

11. functions and operations of irb Only those IRB members who are independent of the clinical trial and the sponsor of the trial should vote/provide opinion in matters related to the study. Only members who participate in the IRB/IEC review and discussion should vote/provide their opinion and advice. The IRB should perform its functions according to written records of its activities and minutes of its meetings, and should comply with GCP and with the applicable regulatory requirements. The investigator may provide information on any aspect of the trial, but should not participate in the deliberations of the IRB or in the vote/opinion of the IRB.

12. FUNCTIONS AND OPERATIONS OF IRB The IRB should establish, document in writing, and follow its procedures , which should include Determining its composition (names and qualifications of the members) Scheduling, notifying its members of, and conducting its meetings Conducting initial and continuing review of trials Determining the frequency of continuing review, as approprite

13. Functions and operations of irb Specifying that no subject should be admitted to a trial before the IRB issues its written approval/favorable opinion of the trial. Specifying that no deviations from, or changes of the protocol should be initiated without prior written IRB approval/favorable opinion of an appropriate amendment, except when necessary to eliminate immediate hazards to the subjects or when the changes involves only logistical or administrative aspects of the trial. specifying that the investigator should promptly report to the IRB.

14. functions and operations of irb Deviations from, or changes of the protocol to eliminate immediate hazards to the trial subjects. Changes increasing the risk to subjects and affecting significantly the conduct of the trial. All adverse drug reactions that are both serious and unexpected. New information that may effect adversely the safety of the subjects or the conduct of the trial.

15. responsibilties of irb An IRB should safeguard the rights, safety and well-being of all trial subjects. The IRB should obtain the following documents. Subject recruirtment procedures (eg: Advertise). Written information to be provided to subjects. Investigator’s Brochure (IRB). Available safety information. Information about payments and compensation. Investigator’s current curriculum vitae. Any other may need to fulfill its responsibilities.

16. responsibilities of irb The IRB/IEC should continuing review of each ongoing trial at intervals appropriate to the degree of risk to human subjects, but at least once per year. The IRB may request more information than is given to study subjects when, in the judgement of the IRB the additional information would add meaning to the protection of the rights, safety and/or well-being of the subjects. The IRB should review both the amount and method of payment to subjects to assure neither compulsion nor undue influence on the trial subjects.

17. responsibilties of irb Payments to a subject should be prorated (day basis) and not wholly contingent on completion of the trial by the subject. The IRB should ensure that information regarding payment to sujects, including the methods, amounts, and schedule of payment to trial subjects , is set forth in the written informed consent from an any other written information to be provided to subjects

18. types of reviews in irb The IRB’s member secretary shall screen te proposals for their completeness and depending on the risk involved categorize them into; EXEMPT REVIEW Includes anonymous surveys. EXPEDITED REVIEW Includes interviews and surveys. FULL BOARD REVIEW Includes any work with vulnerable populations, involving sensitive questions etc........

19. exempt review If the proposed research inolves less than minimal risk to participants and involves any of the following, it may qualify for exempt status. Research conducted in established or commonly accepted educational institutions that specifically involves normal education practices that are not likely to adversely impact students opportunity to learn required educational content. Research that only includes interactions involving educatinal tests, survey procedures, interview procedures or observation of public behaviour. Taste and food quality evaluation and consumer acceptance studies.

20. expedited review If the proposed research presents no more than minimal risk, does not involve any vulnerable populations like children, prisoners, individuals with impaired decision making capacity and economically or educationally disadvantaged persons. and involves any of the following, it may qualify for Expedited review. Collection of data from voice, video, digital or image recordings made for research purposes. Collection of data through noninvasive procedures routinely employed in clinical practice (X-rays). Research involving already approved drugs. When an adverse event or unexpected adverse reaction is reported.

21. full board review All research proposals presenting with more than minimal risk requires full board review. Projects that involves vulnerable population. Collection of blood samples . Prospective collection of biological specimens like sputum, skin appendages, excreta, saliva, amniotic fluid. Procedures that might cause significant psychological or emotional distress. Collection of information about highly sensitive topics . Collection of information that could seriously harm the participant legally, socially, financially etc...

22. decisions of irb Out right approval ( at most, only very minor changes are suggested. The application contained all necessary information) Approval with modification ( there is enough information to judge the study, but clarification or changes are needed) Resubmit with more information ( there is not enough information to judge the application appropriately) Outright disapproval ( there is no way the researcher can ethically to study)

23. informed consent form A major component of GCP is the method by which the researchs will obtain voluntary and informed consent from subjects. Informed consent is a process, not just a form . Information must be presented to enable persons to voluntarily decide whether or not to participate as a research subject. The procedures used in obtaining informed consent should be designed to educate the subjects population in terms that they can understand.

24. informed consent form In seeking informed consent the following information should be provided to the subject. Statement that the study involves research and explanation of the purpose of the research. Expected duration of the subjects participation. Description of the procedures to be followed , including all invasive procedures and, Description of any reasonably risks or discomforts to the subject. Description of any benefits to the subject or others reasonably expected from research. if no benefit expected subject should be made aware of this.

25. informed consent form Disclosure of specific appropriate alternative procedures or therapies available to the subject. Statement describing the extent to which confidentiality of records identifying the subject will be maintained and who will have access to subjects medical records . Trial treatment schedule and the probability for random assignment to each treatment (for randomized trials). Compensation and or treatments available to the subject in the event of a trial related injury. An explanation about whom to contact for trial related queries, rights of subjects and in the event of any injury.

26. informed consent form The anticipated prorated payment, if any, to the subject for participating in the trial. Subject’s responsibilities on participation in the trial. Statement that participation is voluntary, that the subject can withdraw from the study at any time and that refusal to participate will not involve any penalty or loss of benefits to which the subject is otherwise entitled.

27. informed consent form Any other pertinent information which may be required, viz; Statement of foreseeable circumstances under which the subjects participation may be terminated by the investigator without the subject’s consent. Additional costs to the subject that may result from participation in the study. The consequences of a subject’s decision to withdraw from the research and procedures for orderly termination of participation by subject. Statement that the subject or subject’s representative will be notified in a timely manner if significant new findings develop during the course of the research which may affect the subject’s willingness to continue participation by subject. Approximate number of subjects enrolled in the study.

28. indian scenario The DCGI is responsible for regulatory approvals for the conduct of clinical trials in India which is governed by the rules in Amended in Schedule Y . Standard operating procedures for IRB’s are prepared by ICMR. ICMR codes-general principles Essentialiy. Non-Exploitation. Privacy and Confidentiality. Accountability and Transparency. Precaution and Risk minimization. Professional Competence.

29. Ec’S in india-past The requirement for an EC to oversee clinical research was first made in the ICMR policy statement for ethics published in 1980. Several challenges including inadequate formal training, contribution from non-tehnical members, administrative support as well as no SOP’s and a heavy workload were identified. In the absence of regulatory oversight of EC’s the introduction of the clinical trial registry India (CTRI) and self reguation through voulntary accreditation programmes brought a measure of accountability and transparency .

30. ec’s in india-present The years after 2013 brought much transparency and some contol over the constitution and functioning of EC’s which were also entrusted with increasing responsibilty in regulatory trials. The major milestone in the history of EC’s in India was the requirement of registration with Central Drugs Standard Control Organizaton (CDSCO). As on august 1, 2016, there were 1083 Registered EC’s of which 841 were institutional and 242 were independent. Maharashtra has the highest number of EC’s (259) and the least is 1 in sikkim . AP and telangana has 69 EC’s.

31. case study-1 The first case concerned with the widely publicised demonstration project of the human papilloma virus (HPV) vaccine in 2009. Participants in this large project were teenage girls from urban and rural backgrounds living in hostels. A major concern with this study as that informed consent was provided by school heads and hostel wardens in place of assent from the girls and consent from their parents or legally authorized representatives. Parents of the non-resident students could not understand the contents of the brochures and assumed the project as a government intiative. The final result of the study is death of six girls .

32. case study-2 Case described a patient who had been taking a low cost standard treatment for a chronic condition before being enrolled in a study. Because he was feeling better he requested that he be kept on the study drug for a longer period of time but the investigator told him this was not possible. The patient died shortly afterwards . The main concern arising from this study was about post-study access to treatments and whether the participants should have longer access to the study drug when the drug is not yet licensed and has not passed all safety tests for long term use. Alternatively should such patients be provided with a given standard of care for a specified period of time ? should that be a strandard part of a study protocol ?

33. case study-3 Bhopal gas tragedy survivors in covaxin clinical trials. Many of these participants were not aware that they are participating in a drug trail. and atleast tn serious adverse reactions were noted .No informed consent was sought .

34. conclusion There has been a clear spurt in the number of clinical trials being conducted in India. The number of applications recieved by DCGI and IRB’s makes it evident that the clinical trial industry is growing in India. India’s advantages over it’s counterparts are the availability of large multi-ethnic and drug-native patient population, rapid patient recruitment, cost-effective location when compared to western countries. Keeping in mind the rapid growth in clinical trials, EC’s and regulatory bodies in India have been streamlining the processess to protect the well being and the rights of the research participants.

35. conclusion Keeping the future and the stringent quality requirements in mind the Indian regulatory bodies work in par with other governing bodies in par with other governing bodies like ICMR , DBT and AERB in association with agencies like FICCI, FERCAP and SIDCER India is today identified as a major resource centre for conducting trials due to its increased regulatory control. Further investments in the ethical review system and training of clinical invsetigators may assist in improving the level of quality in India’s clinical trial system and build the capacity needed for India to participate in the growing international clinical resarch bussiness .