INDEPENDENT ETHICS COMMITTEE STANDARD OPERATING PROCEDURES€¦ · independent ethics committee standard operating procedures ... independent ethics committee at fortis escorts heart

INDEPENDENT ETHICS COMMITTEE

STANDARD OPERATING PROCEDURES

SOP TITLE: INDEPENDENT ETHICS COMMITTEE

STANDARD OPERATING PROCEDURES (SOPS)

FORTIS HEALTHCARE LIMITED, FORTIS ESCORTS HEART INSTITUTE, NEW DELHI, INDIA

SOP AUTHORS: INDEPENDENT ETHICS COMMITTEE MEMBERS

VERSION: 6; MARCH 11, 2013; REVISION 1; SEPTEMBER 11, 2013

INDEPENDENT ETHICS COMMITTEE AT FORTIS ESCORTS HEART INSTITUTE IS REGISTERED UNDER FEDERAL

WIDE ASSURANCE (FWA) FROM OFFICE OF HUMAN RESEARCH PROTECTIONS (OHRP)

FWA00019835

FWA Expiry : 02/01/2018

IORG0007577

IORG Expiry : 11/07/2015

IRB00009096 Fortis Escorts Heart Institute IRB #2

http://ohrp.cit.nih.gov/search/asearch.asp≠ASUP

CDSCO Reg No: ECR/261/Inst/DL/2013 (Valid till 27 May 2016)

ADMINISTRATIVE OFFICE:

ACADEMICS AND RESEARCH DEPARTMENT

ROOM NO 23 A, IIND FLOOR, RESIDENTIAL TOWER

FORTIS ESCORTS HEART INSTITUTE

OKHLA ROAD, NEW DELHI – 110025

TEL: 91-11-47135138

FAX: 91-11-26825112

E-mail: [email protected]

mailto:[email protected]

Page 1 of 35 Version 6, March 11, 2013; Revision 1, September 11, 2013



CONTENTS

1. INTRODUCTION 2

2. OBJECTIVE 2

3. ROLE AND RESPONSIBILITIES OF COMMITTEE 2

4. OPERATING PROCEDURES 3

4.1. Composition of Committee 3

4.1.1. Scientific Review Committee 4

4.1.2. Appointment, Resignation and Reconstitution 5

4.2. Independent Ethics Committee review fees 6

4.2.1. Fee Structure 6

4.2.2. Budget Preparation 7

4.2.3. Collection 7

4.2.4. Deposits and Accounting 7

4.3. Honorarium 7

4.4. Procedure For Convening A Meeting 7

4.5. Quorum Requirements 8

4.6. Procedure for Submission of Proposal 8

4.7. Documents 9

4.8. Review of Proposals 10

4.8.1. Exemption from review 10

4.8.2. Expedited Review 11

4.8.3. Full Review 13

4.9. Documentation and Records 15

4.10. Notification of Amendments 15

4.11. Notification of Adverse Events 16

4.12. Annual review and Final reporting 18

4.13. Dissolution of Committee 19

4.14. Amending this document 19

5. OTHER FUNCTIONS OF IEC 19

6. APPENDICES 20




1. INTRODUCTION

Academics and Research Department of Fortis Healthcare Limited is establishing an institutional

ethics procedure to review proposals of all research in which members of the FHL (staff and

students), may be involved. It is proposed to have an Institutional Ethics Committee (IEC) based

at the Fortis Escorts Heart Institute as well as at each of the FHL centers. This document has been

prepared to provide information on and streamline the process of obtaining ethics approval for

research projects.

Development of this procedure has been guided primarily by the recommendations made by the

Indian Council of Medical Research (ICMR) in its Guidelines for preparing Standard Operating

Procedures (SOP) for Institutional Ethics Committee for Human Research. In addition we have

referred to the World Health Organization’s (2000) Operational Guidelines for Ethics Committees

that Review Biomedical Research, ICMR‘s (2006) Ethical Guidelines for Biomedical Research on

Human Participants, Code of federal regulation 56.114 as well as the New Gazette of Drugs and

Cosmetics Rules 1945.The Ethics committee needs to be registered under the Drugs Controller

General of India as per the 122 DD rule of the Drugs and Cosmetics Rules 1945.

2. OBJECTIVE

The objective of this SOP is to facilitate the use of Central review process (use of single central

IEC) for the Fortis Network group of Hospitals involved in clinical research activities.

Independent Ethics committee at Fortis Escorts Heart Institute will conduct the central review

process based on the ethical guidelines for biomedical research on human subjects by Indian

Council of Medical Research (ICMR) and Code of federal regulation 56.114. This document shall

put in place a consistent ethical review mechanism for health and biomedical research for all

research proposals received by the Committee. It will ensure that quality and consistency of an

ethical review mechanism is put in place.

3. ROLES AND RESPONSIBILITIES OF COMMITTEE

The purpose of the IEC is to conduct joint review of multi – institutional studies (trials more than

1 Centre) of Fortis Network of Hospitals. Any single centric studies shall be reviewed by the Unit

Ethics committee of the respective Hospitals. Initial decision / Approvals of the multicentric trials

would be taken by CEC which will monitor them from time to time whenever required. All the

proposals shall be submitted as per the SOP. The Committee will review and make unbiased

recommendations on all types of research proposals with a view to safeguard the dignity, rights,

safety and well-being of all actual and potential research participants. The goals of research,

however important, should not be permitted to override the health and well-being of the

research subjects. The Committee will take care that all the cardinal principles of research ethics

viz. Autonomy, Beneficence, Non-maleficence, Proportionality and Justice are adequately taken




care of in planning, conduct and reporting of the proposed research as envisioned in the ICMR

and WHO guidelines. For this purpose, it will look into the informed consent process, risk benefit

ratio, distribution of burden and benefit and provisions for appropriate compensation process

wherever required.

It will review the proposals before start of the study and monitor the research throughout the

study until and after completion of the study through appropriate well documented procedures

for example annual reports, final reports and site visits etc. The committee will also examine

compliance with all regulatory requirements, applicable guidelines and laws.

The mandate of the committee will be to review all research projects involving human

subjects/materials to be conducted at the Institute, irrespective of the funding agency. In

addition, each investigator shall be responsible to committee, for proving the benefit of placing

human subjects at risk. All studies need to be approved before study procedures begin.

4. OPERATING PROCEDURES

4.1. COMPOSITION OF COMMITTEE

The committee shall be multidisciplinary and multisectorial in composition. The Dean, Academics

and Research and other hospital administrative of the Institute are the authorities by which the

Committee is constituted. Independence, competence, pluralism and transparency shall be the

characteristics for IEC. The number of persons in the committee would be kept from 8 to 12

members.

The chairperson of the Committee should not be an employee of this Institute to maintain the

independence of the Committee. The Chairperson will preside over and convene the regular

meetings as well as emergency meetings of the full IEC or a sub-group/committee as required. A

Co-Chairperson (external member) will officiate as well as undertake other responsibilities of the

Chairperson in the absence/non-availability of the Chairperson.

The member secretary will be staff of FEHI and would conduct the business of the Committee

and its meetings in consultation with the Chairperson. The Member Secretary will be in charge of

the Secretariat of the IEC and responsible for reporting to the Chairperson on all matters related

to the IEC.

Other members should be a mix of medical / non-medical scientific and non-scientific persons

including lay public to reflect differing viewpoints. The composition of the IEC has been

constituted keeping in view the guidelines of ICMR and WHO as well as the requirements of the

Schedule Y of Drugs and Cosmetic Acts 1940, as amended, and has the following multi-

disciplinary composition.




The composition and pattern may be as follows: -

1. Chairperson

2. Member-Secretary

3. 1-2 basic scientists ( preferably one pharmacologist )

4. 1-2 clinicians

5. One legal expert or retired judge

6. One social scientist / representative of non-governmental voluntary agency

7. One philosopher / ethicist / theologian

8. One educationist / teacher / intellectual

9. Lay person from the community

Expert Consultants - Subject experts may be invited to offer their views on review of research

protocols. Their inputs will be maintained on record and considered when reaching a decision.

The decision will however be taken by the IEC.

Alternate members shall be invited on a temporary basis to meet the quorum requirement in

case of any emergency to the members who could not make it to the committee meeting.

Special Invitees – The EC can have special invitees, individuals from other specific Institutions or

communities, if required in order to safeguard the interest and welfare of all sections of the

community/society.

Patient Representatives – If considered necessary, based on the requirement of the research

area, representative of specific patient groups or their care givers may be invited, for example,

HIV, Genetic Disorder, etc.

There should be an adequate breadth of representation of gender and community in the

Committee to safeguard the interests and welfare of all sections in general. Members should be

aware of local, social and cultural norms. Attach Appendix A for full list of Members and

qualification.

4.1.1. Scientific Review Committee

Preceding the complete ethics review by committee, the protocol and the accompanying

documents shall be reviewed by the scientific review committee also referred as the Institutional

Review Board, which shall uncover and detail any basic limitations in the material. This shall be a

non-voting entity that shall be constituted by the Institute and institute members with specific

scientific and technical ability to review research protocols. The scientific Review Committee may

have additional temporary members depending on the special protocol review requirements as

adjudged by the Chairperson/Member-Secretary. The committee-members would be bound by a

confidentiality agreement similar to the one binding the ethics committee.




The committee shall be constituted of medical, statistical and specialist reviewers who shall

provide specific inputs regarding the protocols to investigators as well as committee. These

inputs shall be made available to committee at least one week before the final review. See

Appendix B for full list of Members.

4.1.2. Appointment, Resignation and Reconstitution

Terms of Appointment:

Appointment: The Dean, Academics and Research and other hospital administrative shall

constitute the EC keeping in view the broad guidelines as stated above.

Duration: This Committee has been constituted for a period of 4 years i.e., (date). All members,

except the members from Institute shall serve a maximum of four-year term on the committee,

beyond which under exceptional circumstances there may be two incremental extensions for

two years at a time. Extension of membership may be considered due to non-availability of

members of similar stature, qualification and intent to contribute to ethical human testing.

Renewal: Dean, Academics and Research and other hospital administrative will have authority to

continue or replace the existing members after completion of their term. At the end of the term,

1/3 of the IEC members will be replaced such as to maintain the composition. Rotation

(replacement) will start from 5th year of constitution of the IEC.

Replacement: During the tenure, Dean, Academics and Research and other hospital

administrative in consultation with Chairperson/Co-chairperson will have the authority to

replace any of the members in the event that the member has not complied with the conditions

of appointment, is absent without prior information for three consecutive meetings or on an

occurrence of any event which casts a serious doubt on the integrity or ethics of the member.

Conditions of Appointment and Conflict of Interest:

For appointment to the committee, medical scientist and clinicians should have post graduate

qualification and should have had at least 12 years of work experience at positions of significant

responsibility and aware of their role and responsibilities as committee members. Professional

integrity and commitment to human welfare would be important criteria for inclusion as

members. A member should be willing to disclose his/her full name, profession, designation and

affiliations.

After the initial constitution, subsequent appointment to the committee shall be guided by the

quorum requirements and activity of the members involved. Any members who have obvious

undue influence on the decisions of other members by the way of their institutional association,

financial liability, kinship or authority would need to be excluded from the quorum if deemed so




by at least 2 other members. A maximum of three members of the committee shall belong to the

Institute.

A member should declare at the first meeting in which he/she participates, all conflicts of

interest that may compromise his/her position on the EC. It would be up to the rest of the EC to

take an appropriate decision.

A member who has direct involvement or self-affirmed conflict of interest with a proposal being

considered shall not form a part of the quorum.

All EC members should maintain absolute confidentiality of all discussions during the meeting,

including the documents circulated for review, unless required by law. All committee members

and Scientific Review Committee members have to sign a Confidentiality Agreement at the time

of appointment regarding meeting deliberations, applications, information on research

participants and related matters, the term of which shall be binding on them even after the

termination of the contract.

Resignation: If any member wishes to discontinue from the EC he/she would be required to

inform the Dean, Academics and Research in writing Members may voluntarily resign from the

committee at a month’s notice citing appropriate reasons and incase of internal members their

membership would be considered withdrawn, if they resign from the Institute.

4.2. Independent Ethics Committee review Fees

Independent Ethics Committee (IEC) at Fortis Escorts Heart Institute shall charge an application

fee for all industry sponsored human research projects. The Institute shall not charge an EC

application fee.

4.2.1. Fee Structure

Initial Review fee: The EC at Escorts shall charge a non-refundable, Initial Review fee of Rs

50,000 for any single application, and for Fortis multicentric protocols, charges shall be Rs

25,000 per center that will be valid for one year from the date of the project approval.

The initial review fee funds the costs of the initial research review, as well as the costs of

the ongoing review of adverse events, protocol variances and site visits.

Study Renewal fee: The EC at Escorts shall charge a yearly Rs 20,000 for review of all

ongoing projects annually for single centric study and Rs 10,000 per unit for Fortis multi

centric studies the study renewal review fee funds the costs of the Committee renewal

review of the ongoing review of adverse events, protocol variances and site visits. The




committee examines each investigator’s progress reports and activities for the previous

year.

The fee does not apply to federally funded research, investigator initiated research or

research supported by grants from non-profit foundations or organizations. The fee shall

be paid by cheque drawn in favour of “Escorts Heart Institute and Research Centre

Limited”.

4.2.2 Budget Preparation

The Committee review fee should be included as a separate line item in all sponsored budgets or

payment.

4.2.3 Collection

All applications need to be mandatory accompanied by application fee before it can be

processed.

4.2.4 Deposits and Accounting

The EC Member Secretary shall maintain an account of EC application fees invoiced and fees

collected in the EC Office. Deposits shall be made according to Institute Policy. The Member

Secretary shall maintain deposit records with the support of the Ethics Coordinator/ Secretary.

4.3 COMPENSATION AND REIMBURSMENTS

All external members, and experts invited (if any) will be paid an honorarium for each meeting

attended and also receive re-imbursement for travel and other costs incurred towards

contributing to the workings of the IEC, according to the Institution‘s norms.

Appropriate bills and copies of tickets will have to be submitted together with the claim form to

the Secretary.

4.4 PROCEDURE FOR CONVENING A MEETING

Meetings shall be scheduled approximately every two months. At least one meeting in a

calendar month will be held. Exact meeting date shall be notified at least 15 days in advance so

that all members can make themselves available for the purpose.

The member secretary and the EC coordinator/ secretary staff shall be the convener with

responsibility for organizing the meetings, maintaining the records, laying out the agenda and

communicating with all concerned for the meeting. He/ she shall prepare the minutes of the

meetings after incorporating the comments of all the members and get it approved by the

Chairperson before communicating to the Principal Investigator [PI]. In the next meeting, the




first item on the agenda will include (a) an approval of the minutes of the previous meeting and

(b) matters arising from the minutes or action taken reported by the Member Secretary.

All material relevant to the agenda shall be made available to EC and Scientific review

Committee Members at least 2 weeks in advance. Consolidated comments from Scientific

Review Committee shall be made available to the Committee at least one week before the

scheduled date. All decisions will be taken in the meetings by majority vote of members present.

In case of any tie, the Chairperson will have a casting vote. Decisions will not take place by

circulation of project proposals. Any Special Invitees, Patient Representatives and Expert

Consultants called by the EC will not have any part in the decision making/voting, except to

present their specialized/expert view on the subject that they have been requested to address

on by the EC. Participation will require physical presence. For emergency meetings,

videoconferencing and teleconferencing may be considered as options.

4.5 QUORUM REQUIREMENTS

The quorum for decision on a proposal shall be at least five ethics committee members. Keeping

with the revised schedule Y of the Drugs and Cosmetics Act, 1940 (as amended) the committee

approving a research proposal should have in the quorum at least one representative from the

following groups : one basic medical scientist; one clinician; one legal expert; one social scientist

and one lay person from the community. All members should not belong to one gender or one

profession.

4.6 PROCEDURE FOR SUBMISSION AND REVIEW OF PROPOSAL

All proposals should be submitted by the PI in the format prescribed in Appendix E along with

additional accompanying documents (section 4.7). The proposals shall be addressed to the

chairperson of the Ethics Committee, and shall be submitted to the EC coordinator/ Secretary.

The Secretary will communicate with the applicant and will acknowledge receipt of the

application. The Secretary shall screen the proposals for their completeness as well as with

regard to any clarifications or additional documentation that may be required, within a week of

receiving the application (or earlier in case of exemption or expedited review). 12 copies each of

the documents should be submitted as per section 4.7. Any application should be submitted at

least three weeks prior to the next review meeting. A unique submission number shall be

assigned to proposals submitted for review.

Scientific review with suggestions for amendments may be returned to the submitter and the

final submission updated accordingly. In case of significant amendments, a new submission

number may be assigned to the final submission. All members are expected to review the

proposals with adequate attention to Guiding Principles given in Appendix C.




4.7 DOCUMENTS

For a thorough and complete review, all research proposals should be submitted in the following

manner:

Name of the applicant with designation

Name of the Institute / Hospital / Field area where research will be conducted

Name and address of the Sponsor/Funding agency

Approval of the Head of the Department / Institution.

Protocol of the proposed research

Ethical issues in the study and plans to address these issues

Proposal should be submitted with all relevant enclosures like Performa, case report

forms, questionnaires, follow - up cards, etc

Informed consent process, including patient information sheet and informed consent

form in [English, Hindi, and/or any other regional languages as applicable]

For any drug / device trial, all relevant pre-clinical animal data and clinical trial data

from other centres within the country / countries, if available

Curriculum vitae of all the investigators with relevant publications in last five years

Any regulatory clearances required.

Source of funding and financial requirements for the project including compensation.

An agreement to report Adverse Events to EC within 24 hrs of occurrence

Statement of conflicts of interest, if any

Agreement to comply with the relevant national and applicable international

guidelines

A statement describing any compensation for study participation (including expenses

and access to medical care) to be given to research participants; a description of the

arrangements for indemnity, if applicable (in study-related injuries); a description of

the arrangements for insurance coverage for research participants, if applicable; all

significant previous decisions (e.g., those leading to a negative decision or modified

protocol) by other ECs or regulatory authorities for the proposed study (whether in

the same location or elsewhere) and an indication of the modification(s) to the

protocol made on that account. The reasons for negative decisions should be

provided.

An undertaking to submit progress Report once in a year or study period and final

report of the study to EC within a year of completion of the study.

Plans for publication of results – positive or negative- while maintaining the privacy

and confidentiality of the study participants

Any other information relevant to the study




Any available safety information

4.8. REVIEW OF PROPOSALS

4.8.1. Exemption from review

Categories for exemption

The criteria for exemption has been decided based on the National Institute of Health

guidelines8, with adaptations for Indian conditions and within the overall guiding criterion of

minimal risk suggested by the ICMR guidelines, 2006. Accordingly, exemption from review may

be granted to proposals that fall in the category of lower than minimal risk and satisfy one of the

following conditions:

Exemption 1: Research conducted in established or commonly accepted educational settings,

involving normal educational practices, such as (i) research on regular and special education

instructional strategies, or (ii) research on the effectiveness of or the comparison among

instructional techniques, curricula, or classroom management methods.

Exemption 2: Research involving the use of educational tests (cognitive, diagnostic, aptitude,

achievement); survey/interview procedures; observation of public behaviour, unless: (i)

information obtained is recorded in such a manner that human subjects can be identified

directly or through identifiers linked to the subjects and (ii) any disclosure of the human

subjects' responses outside the research could reasonably place the subjects at risk of criminal or

civil liability or be damaging to the subjects' financial standing, employability, or reputation;

Exemption 3: Research involving the collection or study of existing data, documents, records,

pathological specimens, or diagnostic specimens, if these sources are publicly available or if the

information is recorded by the investigator in such a manner that subjects cannot be identified,

directly or through identifiers linked to the subjects. This includes research and demonstration

projects that are designed to study, evaluate, or otherwise examine: (i) public benefit or service

programs (ii) procedures for obtaining benefits or services under those programs (iii) possible

changes in or alternatives to those programs or procedures or (iv) possible changes in methods

or levels of payment for benefits or services under those programs

All primary research data are required to be anonymised and delinked. Details and procedure

for delinking, with information on levels of de-linking should be included in the IEC application.

Research involving vulnerable persons will not be considered for exemption from review.

Vulnerable persons are those who are relatively (or absolutely) incapable of protecting their own

interests. These persons may have insufficient power, intelligence, education, resources,




strength, or other needed attributes to protect their own interests. They may have limited

capacity or freedom to consent or to decline to consent for e.g. children, and persons who

because of mental or behavioural disorders are incapable of giving informed consent.

Procedure for exemption from review

It is the responsibility of the PI to –

a) Identify in the application (see Form VI) for review, the exemption he/she believes is

applicable to the research under consideration

b) Provide a justification for the exemption(s) with sufficient information about the involvement

of human subjects to allow a sufficient assessment that the claimed exemption(s) is appropriate.

A brief description of the proposal (adequate to evaluate risks to subjects and explain criteria

under which exemption is applied for) and the full proposal (with copies of all instruments to be

used, informed consent form) is to be submitted to the Secretary. The proposal is screened by

the Secretary for completeness and sent to the Chairperson. The Chairperson will decide

whether the proposal satisfies the criteria for exemption from review. The IEC members can

request the PI for clarifications on the proposals

If the IEC agrees that the proposal should be exempt from IEC review, the PI should be notified

by the Member Secretary in writing. The letter should clearly mention the applicable provision

given in section 4.8.1 for providing such exemption. If there is a disagreement between

reviewers regarding the exemption, and the proposal cannot be exempt from review, a

recommendation for expedited review or full review may be made by the Chairperson. The

appropriate procedure will then be followed as the case may be.

4.8.2. Expedited review

Proposals that involve no more than minimal risk and those that do not satisfy the criteria for

exemption will be eligible to apply for expedited review. Proposals cannot be considered for

expedited review if identification of the subjects and or their responses would reasonably place

them at risk of criminal or civil liability or be damaging to the subjects financial standing,

employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate

protections will be implemented so that risks related to invasion of privacy and breach of

confidentiality are no greater than minimal. Research involving vulnerable persons may be

considered for expedited review.

Categories for expedited review




Categories of research considered to involve no more than minimal risk, which would be

eligible for consideration for expedited review, are as follows:

1] Already approved studies:

1. Follow-up reports of proposals previously approved either by expedited or full review as long

as the level of risk has not increased since the initial review was undertaken.

2. Minor alterations (which do not result in any increase in risk) to studies which have previously

been approved either by expedited or full review.

New Studies:

1. Research on individual or group characteristics or behaviour (including but not limited to

research on perception, cognition, motivation, identity, language, communication, cultural

beliefs or practices, and social behaviour) or research employing survey, interview, oral history,

focus group, human factors evaluation, or quality assurance methodologies with clear identifiers

to the subject.

Collection of blood samples by finger prick, heel prick, ear prick, or venipuncture from healthy

adults and children.

1. From healthy, non-pregnant adults who weigh at least 50 kg. For these subjects, the

amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur

more frequently than 2 times per week; or

2. From other non-pregnant adults considering the age, weight, and health of the subjects,

the collection procedure, the amount of blood to be collected, and the frequency with

which it will be collected. For these subjects, the amount drawn may not exceed 50 ml or

3 ml per kg in an 8 week period whichever is lesser and collection may not occur more

frequently than 2 times per week.

3. Prospective collection of biological specimens for research purposes by non-invasive

means. Examples include:

(a) Hair and nail clippings in a nondisfiguring manner; (b) deciduous teeth at time of

exfoliation or if routine patient care indicates a need for extraction; (c) permanent teeth,

if routine patient care indicates a need for extraction; (d) excreta and external secretions

(including sweat); (e) uncannulated saliva collected either in an unstimulated fashion or

stimulated by chewing gumbase or wax, or by applying a dilute citric solution to the

tongue; (f) placenta removed at delivery; (g) amniotic fluid obtained at the time of

rupture of the membrane prior to or during labor;




(h) supra- and subgingival dental plaque and calculus, provided the collection procedure

is not more invasive than routine prophylactic scaling of the teeth and the process is

accomplished in accordance with accepted prophylactic techniques; (i) mucosal and skin

cells collected by buccal scraping or swab, skin swab, or mouth washings; (j) sputum

collected after saline mist nebulization.

4. In emergency situations like serious outbreaks or disasters where full review of the

research is not possible. Such research can only be approved as a pilot study or

preliminary work to study the safety and efficacy of the intervention and the same

participants should not be included in the clinical trial that may be initiated on the basis

of the findings of the pilot study. Research on interventions during outbreaks or disasters

may be considered for expedited review provided a Data Safety Monitoring Board

(DSMB) is constituted to review the data.

Disasters create vulnerable persons and groups in society, particularly so in

disadvantaged communities, and therefore, special attention to safety, confidentiality,

usefulness to community must be considered. All international collaborative research in

the disaster-affected area should be done with a local partner on equal partnership basis.

Transfer of biological material, if any, should be as per Government rules taking care of

intellectual property rights issues.

Procedure for expedited review

It is the responsibility of the PI to

1) Indicate in the application for review (Form I), if he/she believes it qualifies for expedited

review; indicate the category under which the review qualifies for expedited consideration

2) In the case of minor protocol amendments of approved research studies clearly specify the

amendments that need expedited review.

The Chairperson will decide whether the proposal satisfies the criteria for expedited review. The

guidelines for review are same as those to be followed for full review (section 4.8.3). If required,

expert opinion may be sought, keeping in mind confidentiality, but the expert will not play any

role in making the final decision. The decision of the expedited review is to be sent in writing by

the Member Secretary to the PI. A list of all research proposals approved using expedited review

procedures is provided to the IEC at its next convened meeting. A record must be maintained of

category under which the expedited review was justified.

4.8.3. Full Review




As recommended in the ICMR, 2006 guidelines, a full review will be undertaken for the following:

1) All research presenting with more than minimal risk.

2) Proposals/protocols that do not qualify for exemption from review or expedited review.

3) Clinical trials that involve vulnerable persons such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons (as detailed above in Section 5.1)

Procedure for full review

The IEC will undertake the full review of proposals at its meetings as per section 4.6.

After the discussion the committee may make one of the following recommendations:

Approval - indicating that the proposal is approved as submitted;

Conditional Approval - indicating that the proposal is approved in principle, subject to the

submission of certain clarifications, minor revisions or additional documents. In this case, the PI

may have to satisfy certain conditions set out by the IEC. This may include the submission of

certain documents. The duration of time by which the PI responds needs to be specified in the

approval letter – and in no case should exceed 3 months. The study can only begin once an

approval letter is issued by the Member Secretary.

Approval after amendment(s) - indicating that the proposal is approved subject to the

incorporation of the specified amendment(s) verified by committee members;

Deferment - indicating that the proposal is not approved as submitted but it can be re-assessed

after revisions, justifications or additional information to address the specified reason(s) for

deferment. The issues of concern are usually of a fundamental nature (e.g. with regard to the

risk/benefit ratio or issue related to participant protection). However, resubmitted proposals will

go under expedited review

Disapproval - indicating that the proposal is not approved because members' concerns for the

protection of the participants have not been satisfactorily addressed even after the revision.

Regardless of the reason for rejection, the IEC must invite the PI to present her/his

views/justification and the same are discussed by the members of the IEC with the PI, and also

among themselves. The rejection letter should explain the reasons underlying the IEC decision.

In case the applicant considers the reasons for disapproval contentious, he/she may appeal for

reconsideration providing justification for appeal. The same application may be reconsidered if

the chairperson believes there is sufficient evidence for the recommendation to be revised.




For multicentric fortis projects, the approval will be sent to the Facility Directors for execution

through unit ethics committee. In case of any operational issues for execution of the projects in

the units, the matter will be brought to the notice of the independent Ethics committee. The

issues raised would be discussed in the next ethics committee meeting.

4.9. DOCUMENTATION AND RECORDS

The proceedings of all meetings shall be documented and shall be kept in confidence. The EC

coordinator/ Secretary shall securely maintain the documentation. The release of the detailed

documentation to non-committee members can only be made in case of exceptional

circumstances, which shall be verified either by court orders or by affirmative opinions by the

Chairperson and the member secretary. All documentation must be retained for at least five

years after the completion of trial. Records should be maintained for the following –

1. The constitution and composition of the committee

2. Standard operating procedures followed by the committee ;

3. Curriculum Vitae (CV) of all members;

4. Copies of the study protocol, data collection formats, case report forms, Investigator’s

brochures etc , submitted for review; All correspondence with committee members and

investigators regarding application, decision and follow up ;

5. Agenda of all EC meetings

- Minutes of all meetings duly signed by the Chairperson;

- Copies of all existing relevant national and international guidelines on research

ethics and laws along with amendments;

- Final report of the Study including microfilms, compact disks or video recordings

All documents mentioned above should be archived for a period of five years from the date of

the completion or termination of the study.

4.10. NOTIFICATION OF AMENDMENTS

Major amendments should not be implemented until they have been reviewed and the decision

of the IEC conveyed to the PI in writing by the Member Secretary. An exception to this situation

is when an immediate change is essential to prevent apparent hazards to research subjects. The

IEC may then be informed as soon as possible of the change which will be reviewed taking usual

considerations into account. In other situations the procedure is as follows:

Amendments sent for expedited review

All amendments may be submitted for expedited review, if the amendments are required before

the proposal comes up for submission of its follow-up report. The procedure in this case is as

detailed for expedited reviews in Section 5.2




Amendments as part of follow-up

Amendments may also be requested at the time the follow-up report is submitted. The

procedure for submission of the follow-up report is as detailed below. . The original proposal

must be resubmitted with the proposed changes (in addition to the follow-up report if submitted

as part of this). An attached list should however mention the changes proposed and the sections

and page numbers in the protocol where these have been detailed. The original proposal needs

to remain unmodified with additions and justifications of changes in the appropriate sections,

being clearly marked so as to be distinguishable from the original. In the situation where the

amendments are sufficiently many/substantive enough to cause fundamental alterations to the

protocol, the IEC may recommend the rewriting of the proposal.

When considering the amendments, the IEC may ask for fresh or re-consent to be taken under

the following conditions:

1) Availability of new information which necessitates deviation from the earlier protocol.

2) When a research participant regains consciousness from an unconscious state or is mentally

competent to understand the study. If such an event is expected then procedures to address it

should be spelt out at the start itself in the informed consent form.

3) In case of studies where a long term follow-up or extension is planned.

4) When there are changes to the modality of treatment/procedures/site visits.

If there is possibility of disclosure of identity through data presentation or photographs which

should be camouflaged adequately) in publications, the fresh/re-consent is to be taken prior to

publication.

The decision on approval/change of status of technical/ethics approval if any given the proposed

amendments, and if necessary, the requirement for a full ethics review, will be conveyed in

writing to the PI by the Member Secretary.

4.11. Notification of Adverse Events

Any event (anticipated or unanticipated) which can affect the rights, welfare or safety of the

participants will be considered an adverse event. These include not only interventions that can

affect participants physically or psychologically but also involving breach of confidentiality (e.g.

loss or theft of data containing subject identifiers). Adverse events can further be classified into

non-serious and serious events. An adverse event is considered serious if it results to -




Death

An event which poses a threat to life

Requiring hospitalization or prolongation in case of existing hospitalization

Resulting in a persistent or significant disability/incapacity

Resulting in a congenital anomaly/birth defect.

An event that requires intervention (surgical or medical) to prevent one of the above outcomes

Breach of confidentiality which may have serious repercussions (e.g. theft of data with identifiers

linked to HIV test results)

An adverse event is considered to be unexpected if it is not identified in nature, severity

or frequency in the current IEC-approved research protocol or informed consent

document.

An adverse event is considered to be associated with the research intervention if there is

a reasonable possibility that the reaction may have been caused by the research

intervention (i.e., a causal relationship between the reaction and research intervention

has a reasonable likelihood).

All serious and unexpected events shall be notified to the Ethics committee as per the 122 DAB

rule in the Drugs and Cosmetics Rules 1945.

In case of any event, the chairperson may decide to call an emergency meeting and discuss

continuation of the study. The completion of quorum in this case would need at least five of the

members of the committee who may make themselves available via teleconferencing or

videoconferencing after receiving appropriate documents.

Following are the possible decisions that the committee may take regarding the continuation of

the study:

Continue without protocol changes

Continue with protocol amendments

Put the study on hold with a methodical withdrawal of suspected treatment(s) till the

cause of events is identified. Such decision may be revised in a subsequent emergency

meeting

Termination of the study

Opinion on financial compensation

Guiding principles for the above recommendations are as follows:




If the committee adjudges the events in question non-serious, the study may continue

without any alteration in the protocol.

If the serious events are a result of breach of protocol, the committee may recommend

disciplinary action against those responsible while allowing the continuation of the study

without changes in the protocol.

If the research process has a reasonable possibility of being the cause of the serious

events in question, the process must be put on hold with a systematic reversal,

safeguarding the health and well-being of the subject while the cause is being

determined. After the cause is identified, the study may continue with appropriate

changes in the study protocol or the committee may recommend termination as

appropriate.

If the event leads to injury or death of the clinical trial participants, he or she shall be

given the compensation as per the 122 DAB rule in the Drugs and Cosmetics Rules 1945

If statistical significance of endpoints has been reached and meaningful inferences can be

drawn, termination of the study must be considered.

If the cause of events cannot be ascertained and the seriousness of adverse events is

such that continuation of the study may pose a significant threat to life or may cause

permanent disability, the committee is obliged to recommend termination.

If the sponsor and the investigators desire termination, the same may be recommended

noting the specific reasons for termination as provided by them.

4.12. Annual Review and Final Reporting

All studies that went through full review process need to submit a follow-up report once a year

(unless lesser intervals are decided on by the IEC) from the date of the start of the study. A

reminder will be sent by the Secretariat to the PI two weeks before the due date of the follow-up

report. If the follow-up report is not received within 4 weeks after the due date, a note will be

sent asking the PI to show cause why the study should not be suspended. Site visits need take

place only in the event of reports of adverse events or violations of human rights. The follow-up

report has to be submitted to the Secretary which will be sent first for technical review and after

getting their approval for any technical alterations, forwarded for ethics review. Apart from the

follow-up report, prior submission of information to the Secretariat may be required in case of a)

Serious Adverse Events (SAE) and b) premature termination of the study. These specific

situations are discussed in separate sections below. The follow-up report needs to give a) details

of progress of the study b) any new information of relevance to the study c) details of proposed

amendments if any; in case of no amendments, this needs to be stated as well. The procedure of

submitting information related to amendments is listed in Section 5.2




The decision on approval/change of status of technical/ethics approval if any, and if necessary,

the requirement for a full ethics review, will be conveyed in writing to the PI by the Member

Secretary. A final report is to be submitted to the Secretariat at the completion of the study. A

reminder will be sent by the Secretariat to the PI one month before the due date of the final

report which is three months after the termination of the study.

The unit Ethics committee shall submit the progress and notification of the termination of the

multi centric Fortis studies to the IEC.

4.13. DISSOLUTION OF COMMITTEE

The committee shall be considered non-functional and dissolution considered in the following

instances:

No meeting is convened for a continuous period of 6 months

Meeting attendance is below 5 independent members for four consecutive meetings

4.14. AMENDING THIS DOCUMENT

Any amendments to this document shall be approved by the authority under which this

committee has been constituted.

5. OTHER FUNCTIONS OF IEC

With the help of Research Unit, the IEC shall also perform the following functions besides

reviewing protocols

Prepare an annual report of activity performed.

Keep itself up-to-date with the latest national and international guidelines and

recommendations on human testing

Maintain and archive the documentation of its members and proceedings

(submissions, approvals, membership list, SAEs, correspondence, agenda and meeting

minutes) for a period of at least 5 years from the last change.




APPENDIX C: GUIDING PRINCIPAL FOR ETHICAL REVIEW

For all research proposals, the Committee will provide technical and ethical assessment, particularly with respect to the:

- Need for carrying out the study in humans

- Acceptability of the research design and study instruments, including the recruitment procedure, the number of subjects, the criteria for subject selection and exclusion, and the criteria for subject or study discontinuation

- Adequacy of toxicological and pharmacological data, for the types, intended dosages and modes of administration of the drugs/devices to be used, and the planned duration of treatment

- Justification for placebo in control arm, if any

- Training and experience of the investigators

- Facilities and infrastructure of study sites

- Adequacy of the clinical research facilities at the study location

- Risks and benefits to the participants

- The manner in which informed consent is obtained, the clarity and comprehensibility of the documentation given to each subject, and assurance that the subject has the right to withdraw from the study at any time without prejudice to his/her further medical treatment

- The certificate of consent including a summarized version of all of the relevant information provided in the documents given to the subject under the main headings of: Purpose of the research; Risks and discomforts; Benefits; Compensation; Alternatives to participation; and Additional items.

- The certificate of consent ending with a paragraph indicating that the subject is fully informed and freely consents to participate in the study

- Assurance that the budget for the project does not include any undue inducement for subject participation, apart from legitimate compensation for travel and lost earnings

- Adequacy of the provisions to protect the confidentiality of data, as for example by omitting information which might lead to the identification of individual subjects, by limiting access to the data, or other appropriate means

- Assurance that the Principal Investigator has signed a statement, forming part of the proposal, that the research will be conducted in conformity with the World Medical Association Declaration of Helsinki, Ethical Principles for Medical Research Involving Human Subjects.




APPENDIX D: WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI

WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI

Ethical Principles for Medical Research Involving Human Subjects

Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the

29th WMA General Assembly, Tokyo, Japan, October 1975

35th WMA General Assembly, Venice, Italy, October 1983

41st WMA General Assembly, Hong Kong, September 1989

48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996

and the 52nd WMA General Assembly, Edinburgh, Scotland, October 2000

Note of Clarification on Paragraph 29 added by the WMA General Assembly, Washington 2002

Note of Clarification on Paragraph 30 added by the WMA General Assembly, Tokyo 2004

INTRODUCTION

1. The World Medical Association has developed the Declaration of Helsinki as a statement of

ethical principles to provide guidance to physicians and other participants in medical

research involving human subjects. Medical research involving human subjects includes

research on identifiable human material or identifiable data.

2. It is the duty of the physician to promote and safeguard the health of the people. The

physician's knowledge and conscience are dedicated to the fulfillment of this duty.

3. The Declaration of Geneva of the World Medical Association binds the physician with the

words, "The health of my patient will be my first consideration," and the International Code

of Medical Ethics declares that, "A physician shall act only in the patient's interest when

providing medical care which might have the effect of weakening the physical and mental

condition of the patient."

4. Medical progress is based on research, which ultimately must rest in part on

experimentation involving human subjects.

5. In medical research on human subjects, considerations related to the well being of the

human subject should take precedence over the interests of science and society.

6. The primary purpose of medical research involving human subjects is to improve

prophylactic, diagnostic and therapeutic procedures and the understanding of the

aetiology and pathogenesis of disease. Even the best-proven prophylactic, diagnostic, and

therapeutic methods must continuously be challenged through research for their

effectiveness, efficiency, accessibility and quality.

7. In current medical practice and in medical research, most prophylactic, diagnostic and

therapeutic procedures involve risks and burdens.

8. Medical research is subject to ethical standards that promote respect for all human beings

and protect their health and rights. Some research populations are vulnerable and need




special protection. The particular needs of the economically and medically disadvantaged

must be recognized. Special attention is also required for those who cannot give or refuse

consent for themselves, for those who may be subject to giving consent under duress, for

those who will not benefit personally from the research and for those for whom the

research is combined with care.

9. Research Investigators should be aware of the ethical, legal and regulatory requirements

for research on human subjects in their own countries as well as applicable international

requirements. No national ethical, legal or regulatory requirement should be allowed to

reduce or eliminate any of the protections for human subjects set forth in this Declaration.

A. BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH

1. It is the duty of the physician in medical research to protect the life, health, privacy, and

dignity of the human subject.

2. Medical research involving human subjects must conform to generally accepted scientific

principles, be based on a thorough knowledge of the scientific literature, other relevant

sources of information, and on adequate laboratory and, where appropriate, animal

experimentation.

3. Appropriate caution must be exercised in the conduct of research, which may affect the

environment, and the welfare of animals used for research must be respected.

4. The design and performance of each experimental procedure involving human subjects

should be clearly formulated in an experimental protocol. This protocol should be

submitted for consideration, comment, guidance, and where appropriate, approval to a

specially appointed ethical review committee, which must be independent of the

investigator, the sponsor or any other kind of undue influence. This 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. The researcher has the obligation to provide monitoring information to the

committee, especially any serious adverse events. The researcher should also submit to the

committee, for review, information regarding funding, sponsors, institutional affiliations,

other potential conflicts of interest and incentives for subjects.

5. The research protocol should always contain a statement of the ethical considerations

involved and should indicate that there is compliance with the principles enunciated in this

Declaration. Medical research involving human subjects should be conducted only by

scientifically qualified persons and under the supervision of a clinically competent medical

person. The responsibility for the human subject must always rest with a medically

qualified person and never rest on the subject of the research, even though the subject has

given consent.




6. Every medical research project involving human subjects should be preceded by careful

assessment of predictable risks and burdens in comparison with foreseeable benefits to the

subject or to others. This does not preclude the participation of healthy volunteers in

medical research. The design of all studies should be publicly available.

7. Physicians should abstain from engaging in research projects involving human subjects

unless they are confident that the risks involved have been adequately assessed and can be

satisfactorily managed. Physicians should cease any investigation if the risks are found to

outweigh the potential benefits or if there is conclusive proof of positive and beneficial

results.

8. Medical research involving human subjects should only be conducted if the importance of

the objective outweighs the inherent risks and burdens to the subject. This is especially

important when the human subjects are healthy volunteers.

9. Medical research is only justified if there is a reasonable likelihood that the populations in

which the research is carried out stand to benefit from the results of the research.

10. The subjects must be volunteers and informed participants in the research project.

11. The right of research subjects to safeguard their integrity must always be respected. Every

precaution should be taken to respect the privacy of the subject, the confidentiality of the

patient's information and to minimize the impact of the study on the subject's physical and

mental integrity and on the personality of the subject.

12. In any research on human beings, each potential subject must be adequately informed of

the aims, methods, sources of funding, any possible conflicts of interest, institutional

affiliations of the researcher, the anticipated benefits and potential risks of the study and

the discomfort it may entail. The subject should be informed of the right to abstain from

participation in the study or to withdraw consent to participate at any time without

reprisal. After ensuring that the subject has understood the information, the physician

should then obtain the subject's freely given informed consent, preferably in writing. If the

consent cannot be obtained in writing, the non-written consent must be formally

documented and witnessed.

13. When obtaining informed consent for the research project the physician should be

particularly cautious if the subject is in a dependent relationship with the physician or may

consent under duress. In that case the informed consent should be obtained by a well-

informed physician who is not engaged in the investigation and who is completely

independent of this relationship.

14. For a research subject who is legally incompetent, physically or mentally incapable of giving

consent or is a legally incompetent minor, the investigator must obtain informed consent

from the legally authorized representative in accordance with applicable law. These groups

should not be included in research unless the research is necessary to promote the health




of the population represented and this research cannot instead be performed on legally

competent persons.

15. When a subject deemed legally incompetent, such as a minor child, is able to give assent to

decisions about participation in research, the investigator must obtain that assent in

addition to the consent of the legally authorized representative.

16. Research on individuals from whom it is not possible to obtain consent, including proxy or

advance consent, should be done only if the physical/mental condition that prevents

obtaining informed consent is a necessary characteristic of the research population. The

specific reasons for involving research subjects with a condition that renders them unable

to give informed consent should be stated in the experimental protocol for consideration

and approval of the review committee. The protocol should state that consent to remain in

the research should be obtained as soon as possible from the individual or a legally

authorized surrogate.

17. Both authors and publishers have ethical obligations. In publication of the results of

research, the investigators are obliged to preserve the accuracy of the results. Negative as

well as positive results should be published or otherwise publicly available. Sources of

funding, institutional affiliations and any possible conflicts of interest should be declared in

the publication. Reports of experimentation not in accordance with the principles laid

down in this Declaration should not be accepted for publication.

ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH MEDICAL CARE

1. The physician may combine medical research with medical care, only to the extent that the

research is justified by its potential prophylactic, diagnostic or therapeutic value. When

medical research is combined with medical care, additional standards apply to protect the

patients who are research subjects.

2. The benefits, risks, burdens and effectiveness of a new method should be tested against

those of the best current prophylactic, diagnostic, and therapeutic methods. This does not

exclude the use of placebo, or no treatment, in studies where no proven prophylactic,

diagnostic or therapeutic method exists.

3. At the conclusion of the study, every patient entered into the study should be assured of

access to the best proven prophylactic, diagnostic and therapeutic methods identified by

the study.

4. The physician should fully inform the patient which aspects of the care are related to the

research. The refusal of a patient to participate in a study must never interfere with the

patient-physician relationship.

5. In the treatment of a patient, where proven prophylactic, diagnostic and therapeutic

methods do not exist or have been ineffective, the physician, with informed consent from




the patient, must be free to use unproven or new prophylactic, diagnostic and therapeutic

measures, if in the physician's judgment it offers hope of saving life, re-establishing health

or alleviating suffering. Where possible, these measures should be made the object of

research, designed to evaluate their safety and efficacy. In all cases, new information

should be recorded and, where appropriate, published. The other relevant guidelines of

this Declaration should be followed.

Note of clarification on paragraph 29 of the WMA Declaration of Helsinki

The WMA hereby reaffirms its position that extreme care must be taken in making use of a

placebo-controlled trial and that in general this methodology should only be used in the absence

of existing proven therapy. However, a placebo-controlled trial may be ethically acceptable, even

if proven therapy is available, under the following circumstances:

Where for compelling and scientifically sound methodological reasons its use is necessary to

determine the efficacy or safety of a prophylactic, diagnostic or therapeutic method; or where a

prophylactic, diagnostic or therapeutic method is being investigated for a minor condition and

the patients who receive placebo will not be subject to any additional risk of serious or

irreversible harm.

All other provisions of the Declaration of Helsinki must be adhered to, especially the need for

appropriate ethical and scientific review.

Note of clarification on paragraph 30 of the WMA Declaration of Helsinki

The WMA hereby reaffirms its position that it is necessary during the study planning process to

identify post-trial access by study participants to prophylactic, diagnostic and therapeutic

procedures identified as beneficial in the study or access to other appropriate care. Post-trial

access arrangements or other care must be described in the study protocol so the ethical review

committee may consider such arrangements during its review.




APPENDIX E: RESEARCH PROTOCOL ORGANIZATION GUIDELINES

RESEARCH PROTOCOL ORGANIZATION GUIDELINES

I. SCOPE OF THIS DOCUMENT

This document lays down a brief outline of sections and headings that are expected to be

present in research protocols being submitted for review. This document is a part of the

documentation for the activities being conducted under the purview of the Research Unit. This

document is guided by recommendations of W.H.O. relating to protocols submitted for review.

II. SECTION HEADINGS

Following are the section headings and brief guidelines on the contents. Though the

arrangement below is not binding, conformance to these will allow speedy review and will

prevent errors of omission in submitted project proposals.

Part 1

Project summary

Like the abstract of a research paper, the project summary, should be no more than 300 words

and at the most a page long (font size 12, single spacing). Provided preferably on a separate

page, it should summarize all the central elements of the protocol, for example the rationale,

objectives, methods, populations, time frame, and expected outcomes. It should stand on its

own, and not refer the reader to points in the project description.

General information

Protocol title, protocol identifying number, and date

Name and address of the sponsor/funding agency

Name and title of the investigator(s) who is (are) responsible for conducting the research, and the address and telephone number(s) of the research site(s), including responsibilities of each.

Name(s) and address (es) of the clinical laboratory (ies) and other medical and/or technical department(s) and/or institutions involved in the research

Rationale & background information

The Rationale specifies the reasons for conducting the research in light of current knowledge. It

should include a well-documented statement of the need/problem that is the basis of the

project, the cause of this problem and its possible solutions. It is the equivalent to the




introduction in a research paper and it puts the proposal in context. It should answer the

question of why and what: why the research needs to be done and what will be its relevance.

The magnitude, frequency, affected geographical areas, ethnic and gender considerations; etc of

the problem should be followed by a brief description of the most relevant studies published on

the subject.

Previous Studies

Published results from in-vitro, animal or human studies should be reported.

References (of literature cited in preceding sections)

References can also be listed at the end of Part 1.

Study goals and objectives

Goals are broad statements of what the proposal hopes to accomplish. They create a setting for

the proposal. Specific objectives are statements of the research question(s). Objectives should

be simple (not complex), specific (not vague), and stated in advance (not after the research is

done). After statement of the primary objective, secondary objectives may be mentioned.

Study Design

The scientific integrity of the study and the credibility of the study data depend substantially on

the study design and methodology. The design of the study should include information on the

type of study, the research population or the sampling frame, and who can take part (e.g.

inclusion and exclusion criteria, withdrawal criteria etc.), and the expected duration of the study

The same study can be described in several ways, and as complete a description of the study as

possible should be provided. For example, a study may be described as being a basic science

research, epidemiologic or social science research, it may also be described as observational or

interventional; if observational, it may be either descriptive or analytic, if analytic it could either

be cross-sectional or longitudinal etc. If experimental, it may be described as a controlled or a

non-controlled study.

Methodology

The methodology section is the most important part of the protocol. It should include detailed

information on the interventions to be made, procedures to be used, measurements to be taken,




observations to be made, laboratory investigations to be done etc. If multiple sites are engaged

in a specified protocol, methodology should be standardized and clearly defined.

Interventions should be described in detail, including a description of the drug/device/vaccine

that is being tested. Interventions could also be in the realm of social sciences for example

providing training or information to groups of individuals.

Procedures* could be biomedical (collection of blood or sputum samples to develop a diagnostic

test), or in the realm of social sciences (doing a questionnaire survey, carrying out a focus group

discussion as part of formative research, observation of the participant's environment, etc.)

*Standardized and/or documented procedures/techniques should be described and

bibliographic references, if not provided earlier should be provided. Instruments which are to be

used to collect information (questionnaires, FGD guides, observation recording form, case report

forms etc.) must also be provided.

In the case of randomized controlled trial additional information on the process of

randomization and blinding, description of stopping rules for individuals, for part of the study or

entire study, the procedures and conditions for breaking the codes etc. should also be described.

A graphic outline of the study design and procedures using a flow diagram must be provided.

This should include the timing of assessments.

Safety Considerations

The safety of research participants is foremost. Safety aspects of the research should always be

kept in mind and information provided in the protocol on how the safety of research participants

will be ensured. This can include procedures for recording and reporting adverse events and

their follow-up, for example. It is useful to remember that even administering a research

questionnaire can have adverse effects on individuals. Procedure for reporting and control of

predictable serious adverse events related to the study must be provided.

Follow-Up

The research protocol must give a clear indication of what follow up will be provided to the

research participants and for how long. This may include a follow up, especially for adverse

events, even after data collection for the research study is completed.




Data Management and Statistical Analysis

The protocol should provide information on how the data will be managed, including data

handling and coding for computer analysis, monitoring and verification. The statistical methods

proposed to be used for the analysis of data should be clearly outlined, including reasons for the

sample size selected, power of the study, level of significance to be used, procedures for

accounting for any missing or spurious data etc. For projects involving qualitative approaches,

specify in sufficient detail how they will be analyzed.

Quality Assurance

The protocol should describe the quality control and quality assurance system for the conduct of

the study, including GCP, follow up by clinical monitors, DSMB, data management etc.

Expected Outcomes of the Study

The protocol should indicate how the study will contribute to advancement of knowledge, how

the results will be utilized, not only in publications but also how they will likely affect health care,

health systems, or health policies.

Dissemination of Results and Publication Policy

The protocol should specify not only dissemination of results in the scientific media, but also to

the community and/ or the participants, and consider dissemination to the policy makers where

relevant. Publication policy should be clearly discussed- for example who will take the lead in

publication and who will be acknowledged in publications, etc. Negative or unexpected findings

are frequently a source for new discoveries therefore their dissemination should be considered

as a case.

Duration of the Project

The protocol should specify the time that each phase of the project is likely to take, along with a

detailed month-by-month timeline for each activity to be undertaken.

Problems Anticipated

This section should discuss the difficulties that the investigators anticipate in successfully

completing their projects within the time frame stipulated and the funding requested. It should

also offer possible solutions to deal with these difficulties.




Project Management

This section should describe the role and responsibility of each member of the team

Ethics

The protocol should have a description of ethical considerations relating to the study. This

should not be limited to providing information on how or from whom the ethics approval will be

taken, but this section should document the issues that are likely to raise ethical concerns. It

should also describe how the investigator(s) plan to obtain informed consent from the research

participants (the informed consent process).

Informed Consent Forms

A description of the informed consent process is required accompanied by copies of informed

consent forms, both in English and the local language in which they are going to be

administered. If the research involves more than one group of individuals, for example

healthcare users and healthcare providers, a separate specifically tailored informed consent

form must be included for each group. This ensures that each group of participants will get the

information they need to make an informed decision. For the same reason, each new

intervention also requires a separate informed consent form.

Part 2

Budget

The budget section should contain a detailed item-wise breakdown of the funds requested for,

along with a justification for each item.

Other support for the Project

This section should provide information about the funding received or anticipated for this

project from other funding organizations.

Collaboration with other scientists or research institutions

Links to other projects

Clearances Required




If the study/trial requires clearance from DCGI / USFDA / ICMR / other regulatory bodies, the

same should be specified.

Curriculum Vitae of investigators

The CV of the Principal investigator and each co-investigator should be provided. In general each

CV should not be more than one page, unless a complete CV is specifically requested for.

Other research activities of the investigators

The Principal investigator should list all current research projects that he/she is involved in, the

source of funding of those projects, the duration of those projects and the percentage of time

spent on each.

Financing and Insurance

Financing and insurance if not addressed in a separate agreement and where relevant should be

described.

Statement of Conflict of Interest

A statement regarding conflict of interest of investigators, if any, must be submitted along with

the protocol.

III. Accompaniments

The investigator along with the protocol must submit following documents wherever

appropriate:

Agreement to comply with Helsinki Declaration and relevant ICH-GCP, DCGI, ICMR and other

regulatory guidelines duly signed by all the investigators. Other guidelines that may be relevant

to the study (e.g. stem cell use guidelines by ICMR for a study using human stem cells) must also

be included as a part of the agreement.

A statement describing any compensation for study participation (including expenses and access

to medical care) to be given to research participants; a description of the arrangements for

indemnity, if applicable (in study-related injuries); a description of the arrangements for

insurance coverage for research participants, if applicable; all significant previous decisions (e.g.,

those leading to a negative decision or modified protocol) by other Ethics Committee or

regulatory authorities for the proposed study (whether in the same location or elsewhere) and




an indication of the modification(s) to the protocol made on that account. The reasons for

negative decisions should be provided.

Agreement to report any serious unexpected research related adverse events to the sponsor

within 24 hours, and IEC within 24 hours and to abide by the recommendations of the

committee relating to the research in consideration

---------X----------