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Standard Operating Procedures of Institutional Ethics Committee

Bhopal Memorial Hospital and Research Centre – EC STANDARD OPERATING PROCEDURES

In Accordance withThe Declaration of Helsinki (2000)

&The ICH GCP (E6) Guideline

&Local Regulations

Effective Date: October 12, 2013

Chairman: Chairman, Ethics Committee, BMHRC Bhopal

Name: Prof. Dr.D. K.Singh

Signature: ______________

Date: ______________

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CONTENTS

1. Goals of EC1.1 Primary Goal of EC1.2 Secondary Goals of EC

2. Role of EC2.1 Region of Supervision of EC2.2 Authority of EC in Overseeing Research Involving Human Subjects

3. EC Membership3.1 EC Members3.2 Member Appointments

4. EC Meetings4.1 EC Meeting Agenda4.2 EC Meeting Procedures4.3 EC Meeting Minutes4.4 EC Notification of Meeting Decisions

5. Review of the Projects Requiring Waiver for Informed Consent Process andDocumentation

5.1 Projects Eligible for Waiver of Written Informed Consent Process5.2 Projects Eligible for Waiver of Requirement for Documentation of the Informed

Consent6. Initial Review by EC of Human Subject Research

6.1 Documents Required for Initial Review6.2 EC Criteria for Approval of New Research6.3 EC Process of Initial Review6.4 Review of External Sites (whenever applicable)

7. EC Monitoring of Human Subject Research in Progress7.1 Amendment Requests7.2 Adverse Event Reports7.3 EC Notification to Institutional Authorities7.4 Additional Measures of EC to Monitor Active Research Projects

8. Research Projects Eligible for Expedited Review and Approval8.1 EC Process for Expedited Review8.2 Research Considered by EC as Suitable for Expedited Review8.3 Previously Approved Research Eligible for Expedited Review

9. Approval of Human Subject Research by Additional Agencies10. EC Records

10.1 EC Documentation10.2 EC Research Projects

Appendix – A: General PrinciplesAppendix – B: Format for Approval of Ethics Committee

BMHRC –EC

In this document, the abbreviation "EC" is used to indicate BMHRC-Ethics Committee forHuman Subject Research.

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1. Goals of EC

1.1 Primary Goal of EC

The primary goal of the EC is to ensure that, in research involving human subjects at BhopalMemorial Hospital and Research Centreor the other institutes overseen by EC (whereverapplicable), the rights and welfare of human subjects are adequately protected. To achievethis goal, the EC will verify whether the research projects are designed in a manner tominimize potential harm to human subjects, review all planned research involving humansubjects prior to initiation of the research, approve research that meets established criteriafor protection of human subjects, and monitor approved research to ascertain that humansubjects are indeed protected. Any research using the human subjects shall follow thegeneral principles referred in Appendix A.

1.2 Secondary Goals of EC

Secondary goals of the EC are to inform and assist Bhopal Memorial Hospital and ResearchCentre or the other institutes overseen by EC (wherever applicable), and its researchers onethical and procedural issues related to the use of human subjects in research, to facilitatecompliance with relevant regulations of the Indian Regulatory Authorities and Indian Councilof Medical Research (ICMR).

2. Roleof EC

1. To conform to ICH GCP guideline E6 and the Declaration of Helsinki and to implement theregulatory procedures mandated by the Indian Regulatory Authorities.

2.1 Region of Supervision of EC

The following categories of research involving human subjects may be initiated only afterreview and Approval by the EC:

a. Research that is to take place on the premises of Bhopal Memorial Hospital andResearch Centre.

b. At its discretion, the EC may accept for review, and approve research projects thatare to take place elsewhere on or off the premises of Bhopal Memorial Hospital andResearch Centre, but only with the involvement of at least one member of the staffof Bhopal Memorial Hospital and Research Centreas an investigator.

2.2 Authority of EC in Overseeing Research Involving Human Subjects

EC is mandated to review and monitor any and all types of research, in which humansubjects are involved. No research involving human subjects at Bhopal Memorial Hospitaland Research Centre will be given exemption from EC review. The authority conveyed to theEC includes the following:

a. To review all research projects involving human subjects.

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b. To approve new research projects, and review continuation of previously approvedprojects and require from investigators revisions in research protocols and informedconsent documents if needed.

c. To disapprove the initiation of a new research project and suspend or terminate apreviously approved project.

d. To monitor the activities in approved projects, in any way deemed necessary,including regularly scheduled continuing review at least every twelve months, andverification of compliance with approved research protocols and informed consentprocedures.

e. To ensure prompt reporting to the EC of any planned changes in approved projects,and to ensure that no material changes occur without prior approval of the EC.

f. To ensure prompt reporting to the EC of any seriousadverse events occurring inapproved projects, or in other projects related in context to the approved projects.

3. EC Composition

3.1 EC Members

EC will conduct its business with the participation of the following persons:

Chairperson – Prof. D. K. Singh, Officer on Special Duty,Trauma CenterInstitute of Medical Sciences, Banaras Hindu University,Varanasi, U.P.

Member – Prof. Manoj Pandey, Director, BMHRC, Bhopal. Member – Dr. Arun Shrivastava, Prof. and Head, Dept. of Pharmacology, Gandhi

Medical College, Bhopal. Member – Dr. Rajnish Joshi, Assistant Professor, Dept. of Medicine, AIIMS,

Bhopal. Member – Sh. Syed Ziaul Hasan Naqvi, Former Principal & Professor, Saifia Law

College, Bhopal. Member – Mrs. Kakoli Roy, Founder & Board Member, “Digdarshika”, Bhopal. Member – Rev. Fr. Daniel Mohitkar, Church of India Anglican, Bhopal. Member – Ms. Vina Puri, Retired Teacher, Carmel Convent, Bhopal. Member Secretary – Dr. Sukhpreet Kaur, Assistant Professor, Dept. of Pathology,

BMHRC, Bhopal.

For each member, the IEC will document the member’s name, qualification, experience,relationship to the institute and member’s role in the IEC.

As mandated by Schedule Y of drug and cosmetic act, India, the EC will have at least sevenmembers.When the primary members or class of primary members are not present for the meetingalternate members can substitute them.

The EC will ascertain that its membership possesses the professional competence necessaryto review human subjects research in all categories encountered at the hospital, includingresearch involving vulnerable population and can judge the acceptability of the research interms of institutional commitments and regulations, applicable law, and standards ofprofessional conduct and practice.

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To be effective and efficient in its operations, and to be responsive to the needs of theresearch community it serves, in its discretion, the EC may increase, above the mandatedminimum, the number of its members. In its discretion, the EC may also reduce itsmembership, as long as the membership conforms to the mandated minimum andcomposition. The EC membership will determine the scope of expertise of its members; toassure appropriate review of the types of applications it receives.

The EC, at its discretion, may invite scientists or non-scientists from within or outside BhopalMemorial Hospital and Research Centre who are not members of the EC, and have specialexpertise to function as co-opted reviewers of a project application, to assist the EC in itsreview process. These co-opted reviewers will have access to all documents submitted tothe EC relevant to the specific project under review, may participate at the deliberationsand make recommendation on the project, but may not vote with the EC.

3.2 Member Appointments

All members will be appointed initially for two-year terms. A member could be re-nominated for a second, consecutive two-year period, as long as a member continues topossess the required qualifications.

4. EC Meetings

EC members will convene bimonthly, to fulfill their mandate to oversee research involvinghuman subjects at Bhopal Memorial Hospital and Research Centre.

4.1 EC Meeting Agenda

The EC will have an agenda for each of its meetings. The agenda will include listing andidentifiers for all research project applications awaiting action by the EC. At least seven daysin advance of the scheduled meeting date, the agenda will be made available by email orpost for review by members of the EC. All documents relating to a study submitted by aninvestigator will be distributed as electronic/paper copies and sent to the members of theEC scheduled to conduct the full review.

4.2 EC Meeting Procedures

The EC will meet bimonthly, to review the research project applications submitted forapproval. With the exception of applications eligible for expedited review (Section 8), the ECmembership will determine the outcome of its review of research project applications atmeetings, where quorum has been established. A quorum requires the presence of aminimum of 5 members at meeting and a vote that includes at least one lay member. Exceptwhen an expedited review procedure is used, the EC will review proposed research atconvened meetings at which a majority of the members of the EC are present, including atleast one member whose primary concerns are in nonscientific areas. In order for theresearch to be approved, it shall receive the approval of a majority of those memberspresent at the meeting. The approval for a particular study is granted for a period of oneyear and the same will be renewed annually after reviewing the study status. IEC has theauthority to define the approval granted for astudy as invalid or expired.The chairperson, orin his absence, another member of the EC will chair the meetings. Whenever a research

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project application is being reviewed, in which a member of the EC may have a conflict ofinterest, that member may leave the site of the EC meeting for the duration of the review ofthat application. If the member with conflict of interest is present will only provide requiredstudy related information and will not be a part of decision making process.

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4.3 EC Meeting Minutes

The Secretary of EC will prepare minutes of each meeting of the EC, during which researchprojects are being reviewed. The minutes will be in sufficient detail, and will include thefollowings:

a. Date and venue of the meetingb. Attendance of members and reason of absence of primary members. If primary

members are absent, the presence of alternate membersc. Decisions reached on each research project application reviewedd. Distribution of membership votes on the decisions, documenting the number of

votes for, against and abstaininge. Reasons for requiring changes in a project, or disapproving, suspending or

terminating a projectf. If vulnerable groups of subjects were included in the research, the justification for

their inclusion, and adequacy of special precautions taken to minimize risksg. Summary of the discussion of disputed issues and their resolutionh. Date of next scheduled continuing review of a project, and the perceived level of risk

on which the time of next review was based

The minutes will be made available for review by the EC members by email and/or post.

4.4 EC Notification of Meeting Decisions

Upon completion of the review of a research project application, the Secretary of EC willprepare a notification document, to inform the applicant principal investigator of theoutcome of the review. This document will include the following information:

a. The outcome of the review by the EC, and the date of decision for approved projectsand the reporting requirements for the principal investigator.

b. For disapproved, suspended or terminated projects, the reasons for these decisions,and the rights of the investigators for rebuttal of the decision.

c. The list of members present in the decision taking meeting and the members whovoted for and against the study. These are listed in the EC Decision Letter send toinvestigator.

5. Review of the Projects Requiring Waiver for Informed Consent Process andDocumentation

5.1 Projects Eligible for Waiver of the Written Informed Consent Process

5.1.1 The EC will consider waiving the requirement of obtaining written informed consentfrom a subject of research, if the nature of the research meets one of the followingdefinitions:

a. Does not violate and is not invasive, andb. Does not involve risks to the subjects that are more than minimal.

Minimal risk means that the probability and magnitude of harm or discomfort anticipated inthe research are not greater in and of themselves than those ordinarily encountered in daily

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life or during the performance of routine physical or psychological examination or tests, i.e.the nature of the research meets one of the following definitions:

i. Research involving collection or study of existing data, documents, records,pathological specimens, or diagnostic specimens, if the investigator records theinformation in such a manner that subjects cannot be identified directly or throughidentifiers linked to the subjects, or if the sources of the information are publiclyavailable.

ii. Research involving normal educational practices.iii. Research involving use of educational tests, survey procedures, interview procedures

or observation of public behavior without revealing subjects' identity, placing themat risk of criminal or civil liability, or damaging their financial standing, employabilityor reputation.

iv. Research that anticipates but lacks definite plans for involvement of human subjects,such as institutional-type centre or training grants; any study involving humansubjects under the umbrella of such grants will have to be reviewed subsequently bythe EC, prior to its initiation.

v. Research that cannot practicably be carried out, if informed consent were to beobtained in advance, provided that the rights and welfare of the subjects will not beadversely affected; in this instance, arrangements shall be made to provide pertinentinformation to the subjects after their participation.

5.1.2 In emergency situations, the EC has right to make exceptions to informed consentrequirements after appropriately reviewing such protocols.

5.2 Projects Eligible for Waiver of the Requirement for Documentation of the InformedConsent

The EC may waive the requirement for documentation of the informed consent (a signedSubject Consent Form), but not that of obtaining informed consent, under one of thefollowing circumstances:

a. The principal research risk is potential harm resulting from a breach ofconfidentiality, and the only record linking the subject and the research is theconsent document.

b. The research presents no more than minimal risk of harm to subjects, and does notinclude any procedure, for which written consent would be required, if it were to beperformed for clinical management. Minimal risk means that the probability andmagnitude of harm or discomfort anticipated in the research are not greater in andof themselves than those ordinarily encountered in daily life or during theperformance of routine physical or psychological examination or tests.

In cases where the EC will waive the requirement for documentation of informed consent,the investigators shall still provide the subject with the written Subject Information Sheetdescribed in Section 5.3 and 5.4, the text of which shall be reviewed and approved by theEC. Based on this information, the investigator shall obtain oral consent to participate, butthe granting of the consent will not be documented in writing.6. Initial Review by EC of Human Subject Research

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An Investigator, who intends to initiate a research project involving human subjects, shall beresponsible for submitting to the EC an application for review and approval of the project,before the project begins. No aspect of use of human subjects in research may begin, untilEC has granted the approval.

6.1 Documents Required for Initial Review

To apply for initial review and approval of a new project, the principal investigator shouldsubmit all documents necessary for an orderly review of the project, particularly thoseaspects involving human subjects. The application shall be accompanied by hard and softcopies each of:

1. Protocol Version <Version No.> dated <Date>.2. Investigator’s Brochure Version <Version No.> dated <Date>.3. Subject Information Sheet and Informed Consent Form <Version No.> dated

<Date> in English.4. Subject Information Sheet and Informed Consent Form <Version No.> dated

<Date> translated from English to Hindi on <Date of Translation>.5. Subject Information Sheet and Informed Consent Form <Version No.> dated

<Date> back translated from Hindi to English on <Date of Back Translation>.6. Proposed methods of subject accrual including advertisement(s), etc7. Principal Investigator’s current CV8. Insurance Policy / Compensation for participation and for serious adverse events

occurring during the study participation.9. Investigator’s Agreement with the Sponsor10. Investigator’s Undertaking11. Approval of the Drug Controller General of India (DCGI) or similar competent

authorities.12. <Other documents such as subject diary, subject emergency card, quality of life

questionnaires, Copyright permissions etc>

6.2 EC Criteria for Approval of New Research

In consideration of approval of a new research project involving human subjects, the EC willreview the application to determine if all of the following criteria are met:a. Risks to subjects are minimizedb. Risks to subjects are reasonable in relation to anticipated benefitsc. Selection of subjects is equitabled. The study is scientifically designed and the sample size has been justifiede. Appropriate informed consent will be sought from prospective subjects or their

legally acceptable representativesf. Informed consent will be appropriately documentedg. There are adequate provisions for monitoring data collected to ensure the safety of

subjects (when appropriate)h. There are adequate provisions to protect the privacy of subjects and to maintain

confidentiality of data (when appropriate)i. Whenever subjects are considered to be vulnerable to coercion or undue influence

(such as children, fetuses, prisoners, pregnant women, mentally ill, intellectuallydisabled, cognitively impaired persons, economically or educationally disadvantaged

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persons), their use is adequately justified and additional safeguards have beenincluded in the study to protect the rights and welfare of these subjects.

Format of EC approval letter would be as shown in Appendix B of the document.

6.3 EC Process of Initial Review

Upon receipt of the documents for an initial review, the Secretary of the EC will notify allmembers. Members would receive a copy of the full protocol and will review the proposalagainst the ninecriteria for approval of research listed in Section 6.2, and include additionalitems on the following: proposed interval until next continuation review, to be based on theestimated extent of risks; whether or not the written informed consent document issufficiently informative and includes all elements of informed consent, and whether andwhat kind of revisions in the protocol or consent document have been or need to beobtained for the application to be approved. Prior to the EC meeting to discuss the project,all EC members will have the authority to request from the applicant Investigator, via theSecretary of EC, revisions or additional information or documents. Upon completing his/herreview, a member could present his / her comments to the EC via the Secretary. Aftersufficient discussion, the members attending the EC meeting will vote on the application, toapprove it, disapprove it, or defer a decision until revisions are implemented, additionalinformation is provided, or further expert review is obtained (including invitation of co-opted reviewers; Section 3.4). The decisions will be based on the votes of all memberspresent. Only those members will vote who are independent the sponsor and are not partof the study team.

Under certain circumstances, if minor revisions in the submitted documents are required ora missing document of minor importance is to be obtained, the EC may delegate thechairperson or the primary reviewer to approve the project on behalf of the EC. Thedecision of the primary reviewer will be ratified in the next full EC meeting.

Depending upon degree of risk involved, the EC may consider monitoring the data and trialactivities to ensure the adequate protection of safety, rights and well-being of participants.

The outcome of any review conducted by the EC will be sent directly to the appropriateInvestigator

In case of disagreement between the EC and the investigators of a project under reviewwith regard to requested revisions or a decision to disapprove the project, the EC willprovide the opportunity of rebuttal for the investigators, either in writing, or by appearingat a meeting of the EC, to defend their cases. Under no circumstances will any subject beadmitted to the trial before the EC issues its written approval/favorable opinion of the trial.

6.4 Review of External Sites (whenever applicable)

If investigator plans to conduct research at external sites that are engaged in research, thefollowing information regarding these sites should be submitted to EC for review:

a. Contact information for the siteb. Site’s permission for the research to be conductedc. Periodic review of documents pertaining to the satellite sites

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Investigator will follow all EC requirements when conducting research at satellite sites.

7. EC Monitoring of Human Subject Research in Progress

The EC will monitor all active research projects involving human subjects, to ascertain thatthe subjects are being protected adequately from research risks and from any otherbreaches of human rights. Regular monitoring of all previously approved projects will be inthe form of continuing reviews scheduled at the time of most recent EC approval of theproject. The frequency of the scheduled continuation reviews will be appropriate to thedegree of risk, but not less than once per year and the schedule of the continuing review willbe decided upon approval. In addition, the EC will ensure that the investigators of activeresearch projects carry out the following, as needed, as a condition of approval of theirprojects:

a. Report to the EC any planned change in the study, and do not implement any changewithout receiving prior approval, except to eliminate immediate hazard.

b. Report to the EC any unanticipated problems involving risks to subjects.c. Report to the EC any new information on the project that adversely influences the

risk/benefit ratio.

7.1 Amendment Requests

Investigators of a previously approved project may request from the EC approval to makeamendments to various aspects of the project. No amendment may be implementedwithout the notification to the EC. An amendment may be in the content or the form ofdocumentation. Types of amendments include the following:

a. Amendment to the study protocolb. Amendment to the investigator's brochure describing a test articlec. Amendment to the informed consent documentd. Amendment to the Investigators involved

Different types of amendments may be requested individually or in combination.Particularly, a change in the study protocol or investigator's brochure may require a changein the informed consent document. The EC will scrutinize the amended documents todetermine the degree to which risks to human subjects may have changed, if there is anyneed to revise the consent document, and if changes in the consent document areadequate. A copy of the current or revised informed consent document shall accompany theamendment application. Administrative changes to the form of documents may not requirefull committee approval (see section 8.3).

7.2 Adverse Event Reports

Investigators of a previously approved project are obligated to report to the EC, anyunexpected adverse event involving human subjects of research. Adverse events occurringat Bhopal Memorial Hospital and Research Centre or at other study sites in a multi-centrestudy must be reported (if requested by the sponsor of a study) to the EC within a week andall SAEs must be reported to EC within 7 working days..

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Adverse events include the following:a. Expected or unexpected harmful effects of an investigational or approved drug,

biologic or device, observed in the approved project, or in other research settingssimilar to that of the approved project

b. Physical or emotional harm to the subject during the execution of the experimentalprotocol

c. An event occurring on the premises of the institution housing the research project,not as a direct result of the research, but in conjunction with it.

The EC will scrutinize the adverse event documents to determine the degree to which risksto human subjects may have changed, if there is any need to revise the consent document,and if changes in the consent document are adequate. A copy of the current or revisedinformed consent document shall accompany the adverse event report.

7.3 EC Notifications to Institutional Authorities

The notification documents will be made available for review by the EC members.

If the study is approved by EC, it will ensure notification to the appropriate institutionalauthorities of:a. Any unanticipated problems involving risks to human subjects or othersb. Any instance of serious or continuing noncompliance with the regulations or the

requirements or determination of the IEC: orc. Any suspension or termination of IEC approval while protecting the rights and

welfare of the study subjects.

7.4 Additional Measures of EC to Monitor Active Research Projects

Additional monitoring of approved projects may occur at the discretion of the EC, intargeted or random form

a. Requests for progress reports from investigators.b. Examinations of research records.c. The EC may consider visiting the institution at any point of study period including a

physical observation of consent process based on the degree of risk involved.d. Verification from sources other than investigators that no material changes in the

study have occurred. In targeting research projects to be subjected to theseadditional monitoring activities, the EC will consider the level of risks of harm, thefrequency and nature of adverse events, the vulnerability of the subjects of research,and any complaints received from the subjects.

If the information gained during its monitoring process indicates that human subjects of aresearch project are exposed to unexpected serious harm, or the requirements of the EC arenot being met, the EC will suspend or terminate the research. In such instances, the EC willprovide the opportunity of rebuttal for the investigators, either in writing, or by appearingat a meeting of the EC to defend their cases.

In most instances, the act of obtaining consent shall be validated on the written documentthat contains the information needed to give informed consent, i.e. the Subject Consent

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Form. The validation shall be implemented by the signatures of the subject or the subject'slegally acceptable representative or impartial witness, and of the investigator obtaining theconsent. In the case of a child being recruited as a subject of research, an assentingsignature of the subject of an age (7 or above) sufficient to comprehend the nature, risksand benefits of the study, shall be obtained on the Subject Consent Form, in addition to thesignature of the legally acceptable representative.

The documentation shall be executed on a single consent form and this original signed formwill be maintained in the study site file. A copy of the executed document shall be given tothe subject or subject's legally acceptable representative. All these information will beverified by the EC, while performing on site visit as additional monitoring in targeted orrandom form.

8. Research Projects Eligible for Expedited Review and Approval

Certain types of research project applications submitted to the EC for initial or scheduledcontinuing review, requests for amendments, or adverse event reports will be eligible for"expedited review". The basic element determining the eligibility for expedited review is themagnitude of the risks to which the human subjects of the research will be exposed.

Only projects involving no more than minimal risk will be considered for expedited review. Ifthe subjects of the research include children, fetuses, pregnant women, mentally ill,intellectually disabled, cognitively impaired persons or prisoners, the project will not beeligible for expedited review, regardless of the risk.

8.1 EC Process for Expedited Review

Expedited review of a new project or previously approved project may be requested by theprincipal investigator at the time of submission of the application, by indicating theapplicable criterion for expedited review. Alternatively, the chairperson may choose toprocess an application by expedited review. Expedited review will be carried out by thechairperson or another experienced member of the EC designated by them. The reviewerwill have the authority to approve the project, without a vote of the EC membership. If thereviewer believes that there is reason for disapproval, or the nature of the project is notsuitable for expedited review, the reviewer will defer any decision, and submit the projectto a full review by the EC. Upon approval, based on expedited review, the EC membershipwill be informed of the approval at the time of a regularly scheduled meeting, and it will berecorded in the minutes of that meeting.

8.2 Research Considered by EC as Suitable for Expedited Review

The following types of research, considered having no more than minimal risk, and notinvolving children, fetuses, pregnant women, prisoners, mentally ill or cognitive impaired orintellectually disabled persons have been explicitly identified as eligible for expeditedreview:

a. Collection of hair and nail clippings in a non-disfiguring manner; deciduous teeth,and permanent teeth if subject care indicates a need for extraction.

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b. Collection of excreta and external secretions including sweat, uncannulated saliva,placenta removed at delivery, and amniotic fluid at the time of rupture of themembrane prior to or during labour.

c. Recording of data from subjects, using non-invasive procedures routinely employedin clinical practice (including use of physical sensors applied either to the surface ofthe body or at a distance and do not involve input of matter or significant amountsof energy into the subject or invasion of the subject's privacy; procedures such asweighing, testing sensory acuity, electrocardiography, electroencephalography,thermography, detection of naturally occurring radioactivity, diagnosticechocardiography, and electroretinography, not including exposure toelectromagnetic radiation outside the visible range, such as X-rays and microwaves).

d. Collection of blood samples by venipuncture, in an amount not exceeding 450milliliters in an eight-week period and no more than two times per week, fromsubjects, who are in good health and not pregnant.

e. Collection of supra-gingival and sub-gingival dental plaque and calculus, provided theprocedure is not more invasive than routine prophylactic scaling of the teeth, and isaccomplished in accordance with accepted prophylactic techniques.

f. Voice recordings made for research purposes, such as investigations of speechdefects.

g. Moderate exercise by healthy volunteers.h. Study of existing data, documents, records, pathological specimens, or diagnostic

specimens.i. Research on individual or group behavior or characteristics of individuals, such as

perception, cognition, game theory, or test development, where the investigatordoes not manipulate subjects' behavior and the research will not involve stress tosubjects.

j. Research on drugs or devices for which an investigational new drug exemption orinvestigational device exemption is not required.

8.3 Previously Approved Research Eligible for Expedited Review

Research approved previously by expedited review will be considered eligible for expeditedreview at the time of its regular continuing review, if during the course of the study; therisks of the study have not increased. Prior to the scheduled date of regular continuingreview, changes may have to be implemented in an approved project. Amendments to apreviously approved research protocol of administrative or logistical nature, revisions in thetext of an informed consent document, or corrections in text of documents, all of which areminor in nature and do not increase the risks involved, will be considered eligible forexpedited review.

9. Approval of Human Subject Research by Additional Agencies

Certain types of research involving human subjects will have to be reviewed and certified byadditional agencies of Bhopal Memorial Hospital and Research Centre as required bygovernment regulatory agencies, sponsors, or the Hospital Authority itself. Depending uponthe type of research, one or more certifications will be a requirement for approval by theEC. To prevent delays in the total review process, at its discretion, the EC may acceptconcurrent review by the EC and the other agency, but defer the final decision until a noticeof certification has been received.

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a. The Bhopal Memorial Hospital and Research Centremay be responsible forsafekeeping, dispensing and monitoring of investigational drugs administered tohuman subjects within the confines of the institution. The same regulations willapply to studies involving marketed drugs and a placebo, being dispensed in ablinded or masked manner. For such drug studies, the EC will require priorcertification by the appropriate hospital pharmacy as a condition for approval.

b. The protocol of research studies involving the administration of radioactivesubstances to human subjects will be reviewed and approved by an appropriatecommittee. When applicable, the EC will require prior certification as a condition forapproval.

c. Research involving tissues from human fetuses will be reviewed and approved by anappropriate committee. For these projects, the EC will require prior certification as acondition for approval.

d. Research projects involving transfer of genetic materials to human subjects will bereviewed and approved by an appropriate committee. The EC will require priorcertification as a condition for approval.

e. All devices, regardless of whether they are investigational or marketed devices, willbe reviewed and approved by an appropriate committee. For studies involvingdevices to be used on or in human subjects, the EC will require prior certification as acondition for approval.

10. EC Records

The EC will retain all relevant documents related to studies submitted to EC for at least fiveyears after completion of the research. These records will be accessible for inspection andcopying by authorized representatives of the regulatory agencies at reasonable times and ina reasonable manner. The documents are maintained in a safe and confidential manner. Noidentifiable information or information that fall within the preview of Intellectual propertyrights will be given to others in right to information act. Any information that is released willbe only after the approval of the committee.

10.1 EC Documentation

The EC will maintain an archive file of all of the following EC documents:

- The Constitution and composition of the EC;- The curriculum vitae of all EC members;- Current national and international guidelines;- Meeting Records- SOPs and Related Documents

10.2 EC Research Projects

The EC will maintain an archive of files for all research projects approved by the EC. Suchfiles will be retained for at least five years after completion of the research. Each projectfolder will include the following types of documents, as conventional hard copy:

a. Copies of the Protocol, data collection formats, CRFs, investigational brochures etc.submitted for review;

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b. All correspondence with EC members and investigators regarding application,decision and follow-up;

c. Agenda of all EC meetings;d. Minutes of all EC meetings with signature of the Chairperson;e. Copies of decisions communicated to the applicants;f. Record of all notification issued for premature termination of a study with a

summary of the reasons;g. Progress reportsh. Final report of the studyi. Investigator’s short CVj. Insurance and Indemnity policy statementk. Certification: Financial Interests and Arrangements of Clinical Investigatorsl. Certification documents from other agencies, as mandated by regulatory agencies or

by Bhopal Memorial Hospital and Research Centreto review and approve a project ofa specific type

m. Texts of advertisements for subject recruitmentn. Notifications of EC decisionso. Reports on amendments and adverse eventsp. Statements on significant new findingsq. Correspondence between EC and investigators of the project.

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APPENDIX – A

GENERAL PRINCIPLES

Any research using the human subjects for medical or scientific research or experimentationshall bear in mind the following principles

I. Principles of essentiality: Whereby, the research entailing the use of humansubjects is considered to be absolutely essential after a due consideration of allalternatives in the light of the existing knowledge in the proposed area ofresearch and after the proposed research has been duly vetted and consideredby an appropriate and responsible body of persons who are external to theparticular research and who, after careful consideration, come to the conclusionthat the said research is necessary for the advancement of knowledge and forthe benefit of all members of the human species and for the ecological andenvironmental well being of the planet.

II. Principles of voluntariness, informed consent and community agreement:Whereby research subjects are fully apprised of the research and the impact andrisk of such research on the research subject and others, and whereby theresearch subjects retain the right to abstain from further participation in theresearch irrespective of any legal or other obligation that may have been enteredinto by such human subjects or someone on their behalf, subject to only minimalrestitutive obligations of any advance consideration receivedand outstanding.Where any such research entails treating any community or group of persons asa research subject these principles of voluntariness and informed consent shallapply, mutatis mutandis, to the community as a whole and to each individualmember who is the subject of the research or experiment. Where the humansubject is incapable of giving consent and it is considered essential that researchor experimentation be conducted on such a person incompetent to give consent,the principle of voluntariness and informed consent shall continue to apply andsuch consent and voluntariness shall be obtained and exercised on behalf of suchresearch subjects by someone who is empowered and under a duty to act ontheir behalf. The principles of informed consent and voluntariness are cardinalprinciples to be observed throughout the research and experiment, including itsaftermath and applied use so that research subjects are continually keptinformed of any and all developments in so far as they affect them and others.However, without in any way undermining the cardinal importance of obtaininginformed consent from any human subject involved in any research the natureand form of the consent and the evidentiary requirements to prove that suchconsent was taken, shall depend upon the degree and seriousness of theinvasiveness into the concerned human subjects person and privacy, health andlife generally and the overall purpose and the importance of the research.

III. Principles of non – exploitation: Whereby as a general rule, research subjectsare remunerated for their involvement in the research or experiment andirrespective of the social and economic condition or status, or literacy oreducational levels attained by the research subjects kept fully apprised of all thedangers arising in and out of the research so that they can appreciate all thephysical and psychological risks as well as moral implications of the researchwhether to themselves or others, including those yet to be born. Such humansubjects should be selected so that the burdens and benefits of the research are

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distributed without arbitrariness, discrimination or caprice. Each research shallinclude an inbuilt mechanism for compensation for the human subjects eitherthrough insurance cover or any other appropriate means to cover all foreseeableand unforeseeable risks by providing for remedial action and comprehensiveafter care, including treatment during and after the research or experiment inrespect of any effect that the conduct of research or experimentation may haveon the human subject and to ensure that immediate recompense andrehabilitative measures are taken in respect of all affected, if and whennecessary.

IV. Principles of privacy and confidentiality: Whereby, the identity and records ofthe human subjects of the research or experiment are as far as possible keptconfidential and that no details about identity of said human subjects, whichwould result in the disclosure of their identity, are disclosed without validscientific and legal reasons which may be essential for the purposes oftherapeutics or other interventions, without the specific consent in writing of thehuman subject concerned, or someone authorized on their behalf; and afterensuring that the said human subject does not suffer from any form of hardship,discrimination or stigmatization as a consequence of having participated in theresearch or experiment.

V. Principles of precaution and risk minimization: Whereby due care and caution istaken at all stages of the research and experiment (from its inception as aresearch idea, its subsequent research design, the conduct of the research orexperiment and its applicative use) to ensure that the research subject andthose affected by it are put to the minimum risk, suffer from no irreversibleadverse effects and generally, benefit from and by the research or experiment,and that requisite steps are taken to ensure that both professional and ethicalreviews of the research are undertaken at appropriate stages so that further andspecific guidelines are laid down, and necessary directions given, in respect ofthe conduct of the research of experiment.

VI. Principles of professional competence: Whereby, the research is conducted atall times by competent and qualified persons who act with total integrity andimpartiality and who have been made aware of and are mindful of, the ethicalconsiderations to be borne in mind in respect of such research or experiment.

VII. Principles of accountability and transparency: Whereby, the research orexperiment will be conducted in a fair, honest, impartial and transparent mannerafter full disclosure is made by those associated with the research or experimentof each aspect of their interest in the research, and any conflict of interest thatmay exist and whereby, subject to the principles of privacy and confidentialityand the rights of the researcher, full and complete records of the researchinclusive of data and notes are retained for such reasonable period as may beprescribed or considered necessary for the purposes of post research monitoring,evaluation of the research, conducting further research (whether by the initialresearcher or otherwise and in order to make such records available for scrutinyby the appropriate level and administrative authority if necessary.

VIII. Principles of the maximization of the public interest and distributive justice:Whereby, the research or experiment and its subsequent applicative use areconducted and used to benefit all human kind and not just those who aresocially better off but also the least advantages, and in particular the researchsubject themselves.

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IX. Principles of institutional arrangements: Whereby there shall be a duty on allpersons conducted with the research to ensure that all the procedures requiredto be complied with and all institutional arrangements required to be made inrespect of the research and its subsequent use or application are duly made in abonafide and transparent manner and to take all appropriate steps to ensurethat research reports, materials and data connected with the research are dulypreserved and archived.

X. Principles of public domain: Whereby the research and any further research,experimentation or evaluation in response to and emanating from such researchis brought into the public domain so that its results are generally made knownthrough scientific and other publications subject to such rights as are available tothe researcher and those associated with the research under the law in force atthat time.

XI. Principles of totality of responsibility: Whereby the professional and moralresponsibility for the due observance of all the principles, guidelines orprescriptions laid down generally or in respect of the research or experiment inquestion, devolves on all those directly or indirectly connected with the researchor experiment including the researchers, those responsible for funding orcontributing to the funding of the research, the institution or institutions wherethe research is conducted and the various persons, groups or undertakings whosponsor, use or derive benefit from the research, market the product (if any) orprescribe its use so that, inter alia, the effect of the research or experiment isduly monitored and constantly subject to review and remedial action at all stagesof the research and experiment and its future use.

XII. Principles of compliance: Whereby, there is a general and positive duty on allpersons, conducting, associated or connected with any research entailing the useof a human subject to ensure that both the letter and the spirit of theseguidelines, as well as any other norms, directions and guidelines which havebeen specifically laid down or prescribed and which are applicable for that areaof research or experimentation, scrupulously observed and duly complied with.

These 12 principles laid down under General Principles are common to all areas ofbiomedical research.

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Appendix – B

Format for Approval of Ethics Committee

<On the letterhead of the Ethics Committee>

<Date>

<Name & Address of Investigator>

Sub: Approval of the Protocol <Protocol No.>

Dear Dr.<Name of Investigator>,

On <Date>, the <state name of the committee, as appropriate> met, reviewed anddiscussed your application dated <Date> to conduct the clinical trial titled“<Title ofProtocol>” <Protocol no.>.

The following documents were reviewed during the meeting:

1. Your Proposal/application letter dated <Date>

2. Protocol Version <Version No.> dated <Date>.

3. Investigator’s Brochure Version <Version No.> dated <Date>.

4. Subject Information Sheet and Informed Consent Form <Version No.>dated <Date> in English.

5. Subject Information Sheet and Informed Consent Form <Version No.>dated <Date> translated from English to <Name of the Language> on<Date of Translation>.

6. Subject Information Sheet and Informed Consent Form <Version No.>dated <Date> back translated from <Name of the Language> to English on<Date of Back Translation>.

7. Proposed methods of subject accrual including advertisement(s), etc

8. Principal Investigator’s current CV

9. Insurance Policy / Compensation for participation and for serious adverseevents occurring during the study participation.

10. Investigator’s Agreement with the Sponsor

11. Investigator’s Undertaking

12. <Other documents such as subject diary, subject emergency card, qualityof life questionnaires>

During its meeting, the EC decided to approve the conduct of the above study in itspresented form <add the clause “subject to obtaining regulatory approval prior to

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enrolling subjects in the study” if applicable>at <name of site> and <name of satellitesites>

The following members of the Ethics Committee were present/voted in the meeting andwere involved in the approval process:

1. <Name> <Role> <Designation>

(e.g. Chairman, Ethics Committee)

2. <Name> <Role> <Designation>(e.g. Member Secretary, Ethics Committee)

3. <Name> <Role> <Designation>

(e.g. basic medical scientists (preferably one pharmacologist)

4. <Name> <Role> <Designation>(e.g. clinicians)

5. <Name> <Role> <Designation>(e.g. legal expert)

6. <Name> <Role> <Designation>

(e.g. social scientist / representative of non-governmental voluntaryagency /philosopher / ethicist / theologian or a similar person)

7. <Name> <Role> <Designation>(e.g. lay person from the community)

It is to confirm that the non-member(s) (additional expertise) <Name><Qualification> waspresent but did not take part in voting procedure. It is also confirmed that neither you norany of the study team members participated in the voting and decision making process.

You are expected to report to the Ethics committee the following:

All deviations from, or changes to, the protocol to eliminate immediate hazards tothe study subjects

Changes that increase the risk to participating subjects and/or those thatsignificantly affect the conduct of the study

All serious adverse events

New information that may affect adversely the safety of the subjects or theconduct of the study

Any changes in the study document

Progress of the study.

Also please provide a report to the Ethics Committee on the completion of the study.

Thanking you,

Yours sincerely,

<Signature><Member Secretary, Ethics Committee>