Tata Memorial Centre
Policy and Procedures Manual
Dr R Batura
TABLE OF CONTENTS
Section 1 Introduction .................................................................................................... 1
1.1 Background Information................................................................................ 1
1.2 History .......................................................................................................... 2
Section 2 Constitution of the Hospital Ethics Committee ................................................ 6
2.1 Mandate of the Hospital Ethics Committee ................................................... 6
2.2 Composition of the Hospital Ethics Committee ............................................. 6
2.3 Membership.................................................................................................. 7
2.4 Terms of appointment................................................................................... 7
2.5 Conditions of appointment ............................................................................ 8
2.6 Officers ....................................................................................................... …9
Section 3 Review ......................................................................................................... 10
3.1 Application requirements ............................................................................ 10
3.2 Elements of Review .................................................................................... 11
3.3 Meeting requirements ................................................................................ 13
3.4 Expedited review.......................................................................................... 13
3.5 Decision making ......................................................................................... 13
3.6 Communicating a decision.......................................................................... 14
3.7 Follow up..................................................................................................…..14
3.8 Documentation and archiving...................................................................…..15
Section 4 Continuing Review of Activities Involving the
Use of Human Subjects ........................................................................ 15
4.1 The Continuing Review Procedure ............................................................. 15
4.2 Amendments to Protocols........................................................................... 16
4.3 Adverse Event Reporting............................................................................ 16
Section 5 Appendices .................................................................................................. 11
Appendix A - Policies
Appendix A-1 Policy on Recruitment of TMC Students and
Appendix A-2 Policy on the Recruitment of Research Subjects.........................24
Appendix A-3 Policy on Research Costs to Subjects………………....................25
Appendix A-4 Guidelines on Compensation for Research Subjects...................26
Appendix A-5 Policy on the Use of Third Party/Surrogate Consent
Appendix A-6 Policy on Blood Withdrawal For Research Purposes...................28
Appendix A-7 Policy for Review of Human Research Involving
Appendix A-8 IND Application Exemption Checklist…………………...................31
Appendix A-9 Procedures for Filing a Notice of Claimed
Investigational Exemption for a New Drug…………………………33
Appendix A-10 Guidelines and Policy on Informed Consent...............................34
Appendix A-11 Policy for Documentation of Informed Consent…………………...37
Appendix A-12 Policy on Reporting Serious Adverse Events Examples
of Categories of Research that may be Reviewed by the
HEC through an ExpeditedReview…………………………………41
Appendix A-13 Health Record Research...........................................................44
Appendix A-14 Guidelines for Research Protocols That Require
Collection and/or Storage of Genetic Materials.......................46
Appendix A-15 Guidelines for Submission and EC Review
of Gene Therapy/Gene Transfer Protocols................................48
Appendix A-16 EC Policy for Data and Safety Monitoring in
Appendix A-17 Policy for Submission of Audit Reports…………………………..54
Appendix B - Forms
Appendix B-1 Adverse Event Reporting Form...................................................59
Appendix B-2 Sample Informed Consent Forms................................................60
Recommended Terms for Use in Consent Forms………………..68
Appendix B-3 Protocol Review Standards.........................................................75
1.1 BACKGROUND INFORMATION
Contemporary models of ethical behavior derive from diverse philosophical roots. Perhaps
the oldest concept in ethics is “virtue”- a human characteristic or habit thought to benefit the
persons possessing it and those around them.
The traits that human societies have valued through the ages have been consistent. Dissimilar
cultures throughout the course of history have agreed in recognising qualities like compassion,
courage, generosity, honesty and self-control as virtues.
The concept of justice and fairness-the equitable treatment of all parties and the avoidance of
favouritism, emerged first as personal virtues and then evolved into a social principal of
reciprocity or the so called “Golden Rule” expressed in many legal, literary, philosophical and
religious texts – Do to others only what you would want others to do to you.
Eighteenth century humanist philosophers Jean-Jacques Rousseau and Immanuel Kant argued
the existence of “human rights”. According to them, all individuals have a basic right to make
choices for themselves and by those choices to define themselves as unique, independent and
special beings, not pawns of the privileged or splinters of a collective whole.
The basic human right derives its strength from numerous subsidiary rights, which gave impetus
to various democratic movements including those that affected the scientific sector:
• The right to the truth – the right to accurate information affecting the choices one makes.
• The right to privacy – the right to conduct one’s life as one pleases, provided it does not
violate the rights of others.
• The right to the care and control of one’s body – the right to avoid personal injury, unless
one freely and knowingly chooses to risk such an injury.
• The right to what has been agreed upon – the right to what others have promised
through free and knowing agreement, oath or contract.
In the nineteenth century, utilitarian philosophers like Jeremy Bentham and John Stuart Mill
proposed a model for analysing the ethics of particular deeds based on a calculation of each
deed’s probable consequences.
1. One should identify the realistic courses of action available
2. One should consider whom each course of action would most benefit and what possible
harm could derive from each
3. One should select the course of action that most likely provides the greatest benefit to
the greatest numbers while posing the least harm to any.
In the twentieth century, existentialist thinkers like Martin Heidegger and Jean-Paul Sartre
suggested that the individual’s absolute freedom of choice and action was the only ethical
The methodology of contemporary clinical research involves three components specifically
designed to address ethical concerns. First, the investigators with their medical and scientific
knowledge and experience are held morally and legally responsible for weighing the risks and
benefits of the research to be pursued and otherwise protecting the human subjects in their
care. Second, the Independent Ethics Committee ensures the protection of the rights and the
well being of participating human subjects. Third, the process of informed consent helps to
safeguard the integrity and liberty of individuals participating in scientific study.
1.2.1 The History Of The Human Subjects Protection System
The modern story of human subjects protections begins with the Nuremberg Code, developed
for the Nuremberg Military Tribunal as standards by which to judge the human experimentation
conducted by the Nazis. The Code captures many of what are now taken to be the basic
principles governing the ethical conduct of research involving human subjects. The first
provision of the Code states "the voluntary consent of the human subject is absolutely
essential." Freely given consent to participation in research is thus the cornerstone of ethical
experimentation involving human subjects. The Code goes on to provide the details implied by
such a requirement: capacity to consent, freedom from coercion, and comprehension of the
risks and benefits involved. Other provisions require the minimization of risk and harm, a
favorable risk/benefit ratio, qualified investigators using appropriate research designs, and
freedom for the subject to withdraw at any time. Similar recommendations were made by the
World Medical Association in its Declaration of Helsinki: Recommendations Guiding Medical
Doctors in Biomedical Research Involving Human Subjects, first adopted by the 18th World
Medical Assembly in Helsinki, Finland, in 1964, and subsequently revised by the 29th World
Medical Assembly, Tokyo, Japan, 1975, and by the 41st World Medical Assembly, Hong Kong,
1989. The Declaration of Helsinki further distinguishes therapeutic from nontherapeutic
1.2.2 The Belmont Report
On September 30, 1978, the National Commission for the Protection of Human Subjects of
Biomedical and Behavioral Research submitted its report entitled "The Belmont Report: Ethical
Principles and Guidelines for the Protection of Human Subjects of Research." The Report,
named after the Belmont Conference Center at the Smithsonian Institution where the
discussions which resulted in its formulation were begun, sets forth the basic ethical principles
underlying the acceptable conduct of research involving human subjects. Those principles,
respect for persons, beneficence, and justice, are now accepted as the three quintessential
requirements for the ethical conduct of research involving human subjects.
Respect for persons involves recognition of the personal dignity and autonomy of individuals,
and special protection of those persons with diminished autonomy.
Beneficence entails an obligation to protect persons from harm by maximizing anticipated
benefits and minimizing possible risks of harm.
Justice requires that the benefits and burdens of research be distributed fairly.
The Report also describes how these principles apply to the conduct of research. Specifically,
the principle of respect for persons underlies the need to obtain informed consent; the principle
of beneficence underlies the need to engage in a risk/benefit analysis and to minimize risks; and
the principle of justice requires that subjects be fairly selected. As was mandated by the
congressional charge to the Commission, the Report also provides a distinction between
"practice" and "research." The text of the Belmont Report is thus divided into two sections: (1)
boundaries between practice and research; and (2) basic ethical principles.
1.2.3 Boundaries Between Practice and Research
While recognizing that the distinction between research and therapy is often blurred, practice is
described as "interventions that are designed solely to enhance the well-being of an individual
patient or client and that have a reasonable expectation of success. The purpose of medical or
behavioral practice is to provide diagnosis, preventive treatment, or therapy to particular
individuals." The Commission distinguishes research as "an activity designed to test an
hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to
generalizable knowledge” (expressed, for example, in theories, principles, and statements of
relationships). Research is usually described in a formal protocol that sets forth an objective and
a set of procedures designed to reach that objective." The Report recognizes that
"experimental" procedures do not necessarily constitute research, and that research and
practice may occur simultaneously. It suggests that the safety and effectiveness of such
"experimental" procedures should be investigated early, and that institutional oversight
mechanisms, such as medical practice committees, can ensure that this need is met by
requiring that "major innovations be incorporated into a formal research project."
1.2.4 Applying the Ethical Principles
Respect for Persons. Required by the moral principle of respect for persons, informed
consent contains three elements: information, comprehension, and voluntariness. First,
subjects must be given sufficient information on which to decide whether or not to participate,
including the research procedure(s), their purposes, risks and anticipated benefits, alternative
procedures (where therapy is involved), and a statement offering the subject the opportunity to
ask questions and to withdraw at any time from the research. Responding to the question of
what constitutes adequate information, the Report suggests that a "reasonable volunteer"
standard be used: "the extent and nature of information should be such that persons, knowing
that the procedure is neither necessary for their care nor perhaps fully understood, can decide
whether they wish to participate in the furthering of knowledge. Even when some direct benefit
to them is anticipated, the subjects should understand clearly the range of risk and the voluntary
nature of participation." Incomplete disclosure is justified only if it is clear that: (1) the goals of
the research cannot be accomplished if full disclosure is made; (2) the undisclosed risks are
minimal; and (3) when appropriate, subjects will be debriefed and provided the research results.
Second, subjects must be able to comprehend the information that is given to them. The
presentation of information must be adapted to the subject's capacity to understand it; testing to
ensure that subjects have understood may be warranted. Where persons with limited ability to
comprehend are involved, they should be given the opportunity to choose whether or not to
participate to the extent they are able to do so, and their objections should not be overridden,
unless the research entails providing them a therapy unavailable outside of the context of
research. Each such class of persons should be considered on its own terms (e.g., minors,
persons with impaired mental capacities, the terminally ill, and the comatose). Respect for
persons requires that the permission of third persons also be given in order to further protect
them from harm.
Finally, consent to participate must be voluntarily given. The conditions under which an
agreement to participate is made must be free from coercion and undue influence. ECs should
be especially sensitive to these factors when particularly vulnerable subjects are involved.
Beneficence. Closely related to the principle of beneficence, risk/benefit assessments "are
concerned with the probabilities and magnitudes of possible harms and anticipated benefits."
The Report breaks consideration of these issues down into defining the nature and scope of the
risks and benefits, and systematically assessing the risks and benefits. All possible harms, not
just physical or psychological pain or injury, should be considered. The principle of beneficence
requires both protecting individual subjects against risk of harm and consideration of not only
the benefits for the individual, but also the societal benefits that might be gained from the
In determining whether the balance of risks and benefits results in a favorable ratio, the decision
should be based on thorough assessment of information with respect to all aspects of the
research and systematic consideration of alternatives. The Report recommends close
communication between the EC and the investigator and EC insistence upon precise answers
to direct questions. The EC should: (1) determine the "validity of the presuppositions of the
research;" (2) distinguish the "nature, probability and magnitude of risk with as much clarity as
possible;" and (3) "determine whether the investigator's estimates of the probability of harm or
benefits are reasonable, as judged by known facts or other available studies."
Five basic principles or rules apply when making the risk/benefit assessment: (1) "brutal or
inhumane treatment of human subjects is never morally justified;" (2) risks should be minimized,
including the avoidance of using human subjects if at all possible; (3) ECs must be scrupulous
in insisting upon sufficient justification for research involving "significant risk of serious
impairment" (e.g., direct benefit to the subject or "manifest voluntariness of the participation" (4)
the appropriateness of involving vulnerable populations must be demonstrated; and (5) the
proposed informed consent process must thoroughly and completely disclose relevant risks and
Justice. The principle of justice mandates that the selection of research subjects must be the
result of fair selection procedures and must also result in fair selection outcomes. The "justness"
of subject selection relates both to the subject as an individual and to the subject as a member
of social, racial, sexual, or ethnic groups.
With respect to their status as individuals, subjects should not be selected either because the
researcher favors them or because they are held in disdain (e.g., involving "undesirable"
persons in risky research). Further, "social justice" indicates an "order of preference in the
selection of classes of subjects (e.g., adults before children) and that some classes of potential
subjects (e.g., the institutionalized mentally infirm or prisoners) may be involved as research
subjects, if at all, only on certain conditions."
Investigators, institutions, or ECs may consider principles of distributive justice relevant to
determining the appropriateness of proposed methods of selecting research subjects that may
result in unjust distributions of the burdens and benefits of research. Such considerations may
be appropriate to avoid the injustice that "arises from social, racial, sexual, and cultural biases
institutionalized in society."
Subjects should not be selected simply because they are readily available in settings where
research is conducted, or because they are "easy to manipulate as a result of their illness or
socioeconomic condition." Care should be taken to avoid overburdening institutionalized
persons who "are already burdened in many ways by their infirmities and environments."
Nontherapeutic research that involves risk should use other, less burdened populations, unless
the research "directly relate[s] to the specific conditions of the class involved."
In February 1980, the Indian Council of Medical Research released a ‘Policy Statement on
Ethical Considerations involved in Research on Human Subjects’ for the benefit of all those
involved in clinical research in India. In 1982, the World Health Organisation (WHO) and the
CIOMS issued the ‘Proposed International Guidelines for Biomedical Research involving
Human Subjects.’ Subsequently the CIOMS brought out the ‘International Guidelines for
Ethical Review in Epidemiological studies’ in 1991 and ‘International Ethical Guidelines
for Biomedical Research involving Human subjects’ in 1993. Over the years, various bodies
in national jurisdictions have also laid down general and specific principles in specific areas of
scientific research entailing the use of human beings as subjects in medical research. These
‘national’ Codes (drawn from the international codes and the universal principles underlying
them) outline ‘guidelines’ to be followed in their respective jurisdictions.
Indian Council Of Medical Research has laid down Ethical Guidelines for Biomedical Research
on Human Subjects in 2000.
2. CONSTITUTION OF THE HOSPITAL ETHICS COMMITTEE (HEC)
The Hospital Ethics Committee is constituted by the authority vested in the Director Tata
Memorial Centre by the Governing Council of the Tata Memorial Centre.
The Hospital Ethics Committee of Tata Memorial Centre was established in 1996 to function in
accordance with ICH and GCP guidelines and those laid down in the Ethical Guidelines for
Biomedical Research on Human Subjects by Indian Council of Medical Research New Delhi.
The HEC was established to formalize and specify the Institution's commitment to promotion of
high ethical standards in patient care, professional education and clinical research, community
The mission of the HEC is to provide a multidisciplinary forum for the analysis and discussion of
ethical standards effecting Tata Memorial Centre in all its activities. This mission is fulfilled
through the Committee’s advisory, educational, policy development, and service functions.
The HEC, through its delegated sub-committees and task forces, is charged with assisting the
Institution in conducting its patient care and operations within a consistent ethical framework and
in the integration of ethical values into practice, policy, relationships, and organizational
The purpose of the IEC is to cultivate a pluralistic and democratic exchange of ethical values
and concerns and to critically analyze that discussion for opportunities to enhance the ethical
integrity of the Institution.
2.1.3 HEC has responsibility within the institution for the following objectives:
o To ensure the competent review and evaluation of all ethical aspects of the research
project received, to ensure compliance with the appropriate laws and safe guard
welfare of subjects.
o Patient care services
o Clinical ethics consultation
o Education of professional, administrative, and support staff about ethical issues
o Continuing education and training programs that assure that HEC members are
qualified to perform their specific duties within the HEC.
The HEC is composed of a Chairperson, a Secretary, and 15-20 active members
who represent an appropriate balance of professional, ethical, legal, cultural,
educational, and community interests. The members will be selected to have an
equitable representation of all specialties in the institution. It includes scientists,
clinicians, members of the community, a lawyer /expert in ethics, a social worker.
There will be adequate representation of age, gender, community, etc. in the
Committee to safeguard the interests and welfare of all sections of the
community / society. Members should be aware of local, social and cultural
norms, as this is the most important social control mechanism.
The committee will comprise a diverse working group without any gender
2.2.1 The following qualities are sought in HEC members:
interest and motivation,
commitment and availability,
experience or education,
respect for divergent opinions,
interest in committee work,
The Hospital Ethics Committee can have as its members, individuals from other institutions or
communities if required. If required, subject experts could be invited to offer their views, for
example for drug trials a clinical pharmacologist, may be included.
2.2.2 The Chairperson of the Committee will necessarily be a person of stature with a scientific
slant and adequate familiarity with the principles of ethics and related issues. He/she will
preferably be from outside the Institution to maintain the independence of the Committee. The
Member Secretary will belong to TMC to conduct the business of the Committee.
2.2.3 The composition may be as follows:-
2. 1-2 basic medical scientists.
3. 1-2 clinicians from each specialty
4. One legal expert or retired judge
5. One social scientist / representative of non-governmental voluntary agency
6. One philosopher / ethicist / theologian
7. One lay person from the community
8. Member Secretary
•All members are nominated by the Director TMC in consultation with the
Chairperson and Member, Secretary.
•Conflictof interest will be avoided when making appointments, but where
unavoidable there will be transparency with regard to such interests.
•A rotation system for membership will be followed that allows for continuity, the
development and maintenance of expertise within the EC, and the regular input of
fresh ideas and approaches.
•Alternate members may be appointed in case of prolonged absence of a standing
member with the concurrence of the Committee Members.
2.4 TERMS OF APPOINTMENT
The members of the Tata Memorial Hospital Ethics Committee will be appointed for
duration of 2 years.
The membership may be renewed after the stated term of 2 years.
2.4.3 Replacement procedure
The members may be replaced at the discretion of the appointing authority for the same.
2.4.4 Removal procedure
A member may be relieved of his/her membership in case of a of conduct unbecoming
for a member of the Ethics Committee or inability to participate in the meetings on any
2.4.5 Voting status
All nominated members have the right to vote.
2.5 CONDITIONS OF APPOINTMENT
2.5.1 Name, age, gender, profession, and affiliation will be publicized whenever the
committee is reconstituted or there is a change in the membership.
2.5.2 Conflict of interest to be disclosed if any exists.
2.5.3 Members must apprise themselves of the relevant documents, codes, GCP, ICH
guidelines and the ICMR code.
2.5.4 An investigator can be a member of the EC; however, the investigator-as-member
cannot participate in the review and approval process for any project in which he or she has
a present or potential conflict of interest.
The Ethics Committee will have the following Office bearers who have the expertise
and professional qualification to review what comes in.
The HEC chairperson should be a highly respected individual preferably from outside the
institution, fully capable of managing the HEC and the matters brought before it with fairness
and impartiality. The task of making the HEC a respected part of the institutional community
will fall primarily on the shoulders of this individual. The HEC must be perceived to be fair
and impartial, immune from pressure either by the institution's administration, the
investigators whose protocols are brought before it, or other professional and
The Secretary will be a senior member of the staff, committed to the task of coordinating and
managing the activities of the committee. He/she will be responsible for scheduling the
meetings, describing the agenda and ensuring that the function of the committee is
conducted as per the norms and policies described in this manual.
2.7 QUORUM REQUIREMENTS
More than half the minimum number of members is required to be present to compose a
At least one Representative of each major clinical specialty, Social worker,
Secretary/Chairperson must be present to constitute a quorum; no quorum should consist
entirely of members of one profession or one gender; a quorum should include at least one
member whose primary area of expertise is in a non-scientific area, and at least one member
who is independent of the institution/research site.
2.8 INDEPENDENT CONSULTANTS
The HEC may call upon, or establish a standing list of, independent consultants who may
provide special expertise to the HEC on proposed research protocols. These consultants may
be specialists in ethical or legal aspects, specific diseases or methodologies, or they may be
representatives of communities, patients, or special interest groups.
2.9 EDUCATION FOR HEC MEMBERS
HEC members have a need for initial and continued education regarding the ethics and
science of biomedical research.
All EC members must be conversant with GCP guidelines, ICH and ICMR guidelines for
research involving human subjects.
HEC members will receive introductory training material in the work of an HEC as well as
ongoing opportunities for enhancing their capacity for ethical review.
A qualified researcher responsible for the ethical and scientific conduct of the research should
submit an application for review of the ethics of proposed biomedical research.
All documentation required for a thorough and complete review of the ethics of proposed
research should be submitted by the applicant.
signed and dated application form;
the protocol of the proposed research clearly identified and dated, together with
supporting documents and annexure;
a summary in non-technical language, synopsis, or diagrammatic representation
(‘flowchart’) of the protocol;
a description of the ethical considerations involved in the research;
case report forms and other questionnaires intended for research participants;
when the research involves a study product such as a pharmaceutical or device under
investigation, an adequate summary of all safety, pharmacological, pharmaceutical ,and
toxicological data available on the study product, together with a summary of clinical
experience with the study product to date e.g., recent investigator’s brochure, published
data, a summary of the product’s characteristics;
investigators’ curriculum vitae updated, signed, and dated;
material to be used including advertisements for the recruitment of potential research
a description of the process used to obtain and document consent; written and other
forms of information for potential research participants clearly identified and dated in the
languages understood by the potential research participants;
informed consent form clearly identified and dated in and in English, Hindi and Marathi ;
budget allocation as per the TMH format
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;
a description of the arrangements for insurance coverage for research participants, if
a statement of agreement to comply with ethical principles set out in relevant guidelines;
all significant previous decisions (e.g., those leading to a negative decision or modified
protocol by other HECs or regulatory authorities for the proposed study whether in the
same location or elsewhere and an indication of modifications to the protocol made on
that account. The reasons for previous negative decisions should be provided.
All properly submitted applications will be reviewed within four weeks and according to the
established review procedure.
3.2 ELEMENTS OF THE REVIEW
The primary task of the HEC lies in the review of research proposals and their supporting
documents, with special attention given to the informed consent process, documentation, and
the suitability and feasibility of the protocol. HEC will take into account prior scientific review by
the Scientific Review Committee, and the requirements of applicable laws and regulations.
The following will be considered, as applicable:
3.2.1 Scientific Design and Conduct of the Study
the appropriateness of the study design in relation to the objectives of the study, the
statistical methodology (including sample size calculation), and the potential for reaching
sound conclusions with the smallest number of research participants;
the justification of predictable risks and inconveniences weighed against the anticipated
benefits for the research participants and the concerned communities;
the justification for the use of control arms;
criteria for prematurely withdrawing research participants;
criteria for suspending or terminating the research as a whole;
the adequacy of provisions made for monitoring and auditing the conduct of the
research, including the constitution of a data safety monitoring board (DSMB);
the adequacy of the site, including the supporting staff, available facilities, and
the manner in which the results of the research will be reported and published;
3.2.2 Care and Protection of Research Participants
the suitability of the investigators’ qualifications and experience for the proposed study;
any plans to withdraw or withhold standard therapies for the purpose of the research,
and the justification for such action;
the medical care to be provided to research participants during and after the course of
the adequacy of medical supervision and psycho-social support for the research
steps to be taken if research participants voluntarily withdraw during the course of the
the criteria for extended access to, the emergency use of, and/or the compassionate use
of study products;
the arrangements, if appropriate, for informing the research participant’s general
practitioner or family doctor, including procedures for seeking the participant’s consent
to do so;
a description of any plans to make the study product available to the research
participants following the research;
a description of any financial costs to research participants; the rewards and
compensations for research participants (including money, services, and/or gifts);
the provisions for compensation/treatment in the case of the injury/disability/death of a
research participant attributable to participation in the research;
the insurance and indemnity arrangements;
3.2.3 Protection of Research Participant Confidentiality
a description of the persons who will have access to personal data of the research
participants, including medical records and biological samples;
the measures taken to ensure the confidentiality and security of personal information
concerning research participants.
3.2.4 Informed Consent Process
a full description of the process for obtaining informed consent, including the
identification of those responsible for obtaining consent;
the adequacy, completeness, and understandability of written and oral information to be
given to the research participants, and, when appropriate, their legally acceptable
clear justification for the intention to include in the research individuals who cannot
consent, and a full account of the arrangements for obtaining consent or authorization
for the participation of such individuals;
assurances that research participants will receive information that becomes available
during the course of the research relevant to their participation including their rights,
safety, and well-being;
the provisions made for receiving and responding to queries and complaints from
research participants or their representatives during the course of a research project.
3.2.5 Community Considerations
the impact and relevance of the research on the local community and on the concerned
communities from which the research participants are drawn;
the steps taken to consult with the concerned communities during the course of
designing the research;
the influence of the community on the consent of individuals;
proposed community consultation during the course of the research;
the extent to which the research contributes to capacity building, such as the
enhancement of local healthcare, research, and the ability to respond to public health
a description of the availability and affordability of any successful study product to the
concerned communities following the research;
the manner in which the results of the research will be made available to the research
participants and the concerned communities.
3.2.6 Recruitment of Research Participants
the characteristics of the population from which the research participants will be drawn
(including gender, age, literacy, culture, economic status, and ethnicity);
the means by which initial contact and recruitment is to be conducted;
the means by which full information is to be conveyed to potential research participants
or their representatives;
inclusion criteria for research participants;
exclusion criteria for research participants.
3.3 MEETING REQUIREMENTS
HEC will meet at 8.30 am on the last Friday of every month unless otherwise specified.
The meeting requirements are:
3.3.1 HEC members will be given all the relevant documents at least one week in advance of
the meeting for review;
3.3.2 Meetings will be minuted and the minutes approved in the subsequent meeting;
3.3.3 The applicant, sponsor, and/or investigator may be invited to present the proposal or
elaborate on specific issues;
3.4.4 Independent consultants may be invited to the meeting or to provide written comments,
subject to applicable confidentiality agreements.
3.4 EXPEDITED REVIEW
An expedited review procedure consists of a review of research involving human subjects by the
HEC chairperson or by one or more experienced reviewers designated by the chairperson from
among members of the HEC.
Research activities that
present no more than minimal risk to human subjects, and
involve only procedures listed in one or more of the categories, may be reviewed by the
HEC through the expedited review procedure. (See Appendix 13 for details)
A brief summary and review decision of the protocol will be placed before the HEC members in
the next meeting.
The expedited review procedure may not be used where 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.
The expedited review procedure may not be used for classified research involving human
The standard requirements for informed consent (or its waiver, alteration, or exception) apply
regardless of the type of review, expedited or convened, utilized by the HEC.
In making decisions on applications for the ethical review of biomedical research, the HEC will
take the following into consideration:
3.5.1 A member will withdraw from the meeting for the decision procedure concerning an
application where there arises a conflict of interest; the conflict of interest should be indicated to
the chairperson prior to the review of the application and recorded in the minutes;
3.5.2 Decision may only be taken when sufficient time has been allowed for review and
discussion of an application in the absence of non-members (e.g., the investigator,
representatives of the sponsor, independent consultants) from the meeting, with the exception
of EC staff.
3.5.3 Decisions will only be made at meetings where a quorum is present.
3.5.4 The documents required for a full review of the application should be complete and the
relevant elements considered before a decision is made.
3.5.5 Only members who participate in the review will participate in the decision.
3.5.6 Decisions will be arrived at through consensus, where possible; when a consensus is not
possible, the HEC will vote.
3.5.7 Any advice that is non-binding will be appended to the decision.
3.5.8 In cases of conditional decisions, clear suggestions for revision and the procedure for
having the application re-reviewed will be specified.
3.5.9 A negative decision on an application will be supported by clearly stated reasons.
3.6 COMMUNICATING A DECISION
A decision will be communicated in writing to the applicant, preferably within two weeks’ time of
the meeting at which the decision was made.
3.6.1 The communication of the decision will include, but is not limited to, the following:
the exact title of the research proposal reviewed;
the clear identification of the protocol of the proposed research or amendment, date and
version number (if applicable).
the names and specific identification number version numbers/dates of the documents
reviewed, including the potential research participant information sheet/material and
informed consent form;
the name and title of the applicant;
the name of the site(s);
the date and place of the decision;
a clear statement of the decision reached;
any advice by the HEC;
in case of a conditional decision, any requirements by the HEC, including suggestions
for revision and the procedure for having the application re-reviewed;
in the case of a positive decision, a statement of the responsibilities of the applicant; for
example, confirmation of the acceptance of any requirements imposed by the HEC;
submission of progress report(s); the need to notify the HEC in cases of protocol
amendments (other than amendments involving only logistical or administrative aspects
of the study); the need to notify the HEC in the case of amendments to the recruitment
material, the potential research participant information, or the informed consent form; the
need to report serious and unexpected adverse events related to the conduct of the
study; the need to report unforeseen circumstances, the termination of the study, or
significant decisions by other HEC; the information the HEC expects to receive in order
to perform ongoing review; the final summary or final report;
the schedule/plan of ongoing review by the DSMSC;
in the case of a negative decision, clearly stated reason(s) for the negative decision;
signature (dated) of the chairperson (or other authorized person) of the HEC.
HEC will follow-up progress of all studies for which a positive decision has been reached, from
the time the decision was taken until the termination of the research.
3.7.1 Follow-up procedure:
The follow-up review intervals will be determined by the nature and the events of research
projects, though each protocol will undergo a follow-up review at least once a year.
The Data and Safety Monitoring Subcommittee will undertake the follow up process and forward
the recommendations to the HEC. The process is described in the SOP for the Data and Safety
3.7.2 A decision of a follow-up review will be issued and communicated to the applicant,
indicating a modification, suspension, or termination of the HEC’s original decision or
confirmation that the decision is still valid.
3.7.3 In the case of the premature suspension/termination of a study, the applicant must notify
the HEC of the reasons for suspension/termination.
3.7.4 A summary of results obtained in a study prematurely suspended/terminated should be
communicated to the HEC.
3.7.5 HEC should receive notification from the applicant at the time of the completion of a study
3.7.6 HEC should receive a copy of the final summary or final report of a study.
3.8 DOCUMENTATION AND ARCHIVING
All documentation and communication of HEC will be dated, filed, and archived. Documents be
archived for a minimum period of 3 years following the completion of a study.
3.8.1 Documents that will be filed and archived include, but are not limited to,
the constitution, written standard operating procedures of the HEC, and regular (annual)
the curriculum vitae of all HEC members;
a record of all income and expenses of the HEC, including allowances and
reimbursements made to the secretariat and HEC members;
the published guidelines for submission established by the HEC;
the agenda of the HEC meetings;
the minutes of the HEC meetings;
one copy of all materials submitted by an applicant;
the correspondence by HEC members with applicants or concerned parties regarding
application, decision, and follow-up;
a copy of the decision and any advice or requirements sent to an applicant;
all written documentation received during the follow-up;
the notification of the completion, premature suspension, or premature termination of a
the final summary or final report of the study.
4. THE CONTINUING REVIEW OF ACTIVITIES INVOLVING THE USE OF
4.1 THE CONTINUING REVIEW PROCEDURE
Any research activity involving the use of human subjects that has received initial review
and approval by HEC is subject to continuing review and approval. Time intervals for
such reviews shall be made at the discretion of the Data and Safety Monitoring
Subcommittee but shall occur no less than annually.
4.2 AMENDMENTS TO PROTOCOLS
Amendments to protocols or consent forms must be requested in writing, and reviewed
and approved by the HEC prior to making any changes in study procedures. Requests
must describe what modifications are desired, why the changes are required, and if the
changes pose any additional risks to the subjects. Minor changes (those that do not
increase the risk or decrease the potential benefit to subjects) may be administratively
approved. Changes considered to be more than minor must be reviewed at a convened
meeting of the HEC. All amendments are reported to, discussed and approved by the
HEC at a convened meeting.
4.3 SERIOUS ADVERSE EVENT REPORTING
When a subject who is participating in a research study experiences an unexpected or
serious adverse event, the PI must promptly report the incident to the Data and Safety
Monitoring Subcommittee of the HEC. A summary of the adverse event must be
submitted to the Data and Safety Monitoring Subcommittee of the HEC. For adverse
events or reactions that occur at TMC the following apply (hospitalization for any reason
must be reported):
• If the adverse event or reaction was anticipated in the protocol and the subject was
informed about the possibility of the event in the consent form, there is no need to
inform the Data and Safety Monitoring Subcommittee of the HEC unless the adverse
event was unexpectedly serious, life threatening, or fatal.
• If the adverse event or reaction was unanticipated, unexpectedly serious, life-
threatening or fatal, the adverse event must be reported to the Data and Safety
Monitoring Subcommittee of the HEC office within 24 hours. If the adverse event
occurs after hours or on a week-end, notification should be sent to the Secretary
Data and Safety Monitoring Subcommittee of the HEC at the extension 7109.
• If the research study is being supported by an industry sponsor, the PI is also
responsible for notifying the sponsor. The sponsor must then notify the regulatory
authorities within 24 hours.
• If the PI holds the Investigational New Drug (IND) or Investigational New Device
Exemption (IDE) in his/her name, he/she is required to notify the regulatory
authorities of the adverse event or reaction within 24 hours, in addition to notifying
the Data and Safety Monitoring Subcommittee of the HEC.
• Notifying the Data and Safety Monitoring Subcommittee of the HEC does not relieve
the PI from his/her responsibility to notify the sponsor, regulatory authorities.
A Within 10 working days, the PI must submit a written report of the adverse event or reaction
to the Data and Safety Monitoring Subcommittee of the HEC in the specified format.
For industry sponsored research trials of drugs or devices, sponsors are required to
inform investigators of adverse events or reactions that occur at other sites. When PIs
are informed of the adverse events in sponsor safety memos and other correspondence,
the PI must review the adverse event report and then notify the Data and Safety
Monitoring Subcommittee of the HEC. This should be done as promptly as possible after
receipt of the report from the sponsor.
POLICY ON RECRUITMENT OF
TMC STUDENTS AND STAFF FOR RESEARCH
“Student” means any individual who is enrolled at TMC and those individuals who are in
training as, Residents, Fellows, or Postdoctoral trainees, including individuals enrolled at
a training facility other than TMC training or work program.
“Staff” means all other TMC employees, including faculty.
TMC students and staff have the same rights as any other potential subject to participate
in a research project, irrespective of the degree of risk, provided all of the following
• The research must not bestow upon participating TMC subjects any competitive
academic or occupational advantage over other TMC students or staff who do
not volunteer, and the researchers must not impose any academic or
occupational penalty on those TMC students or staff who do not volunteer.
• TMC students and staff must not be systematically treated differently from non-
TMC subjects as part of the project.
• Due to the potential for perceived or real coercion to participate, TMC students
and staff who desire to participate in the research (especially those under the
direct supervision of the principal investigator or listed research collaborators)
must be reviewed by Director TMC.
POLICY ON THE RECRUITMENT OF RESEARCH SUBJECTS
SPECIFIC RECRUITMENT GUIDELINES
(1) In addition to its review for scientific merit and protection of subjects from
unnecessary research risks, the HEC will evaluate all protocols for subject
recruitment especially with respect to women with childbearing potential, minority
groups and children. Exclusion of minorities, women or children will be
recommended or approved when inclusion is inappropriate with respect to the
health of the subjects or the purpose of the research.
(2) TMC PATIENTS - Patients may be identified as potential research subjects through
direct contact of the PI with his or her patients, collaboration with physicians of other
medical specialties, contact with individual attending physicians, posted written
notices, radio announcements, or other HEC approved methods.
a. Inpatients - May be recruited by the investigator or other member of the research
team only after consultation with the patient's attending physician.
b. Outpatients -
(i)For minimal risk research which does not bear directly upon a specific
continuing therapeutic relationship between the individual and a TMC physician,
outpatients may be recruited* without prior notification of their personal
physicians. However, when possible, each subject’s personal physician should
be notified of the study and informed that the patient has been entered into a
minimal risk study.
(ii)For more than minimal risk research or any research bearing directly upon a
specific diagnosis or treatment, the subject’s personal physician should be
notified before enrolling* the subject.
* If the potential research subject is a minor, then contact must be via a parent or
POLICY ON RESEARCH COSTS TO SUBJECTS
If a research participant may have to bear any costs, which would be unnecessary if the
subject had declined to participate in the research, all potential subjects must be fully
informed of the nature and estimated extent of these costs when obtaining consent.
Examples of additional research costs include:
1) Prolongation of treatment or hospitalization.
2) Extra diagnostic tests necessary for the research.
3) Extra clinical or laboratory assessments to evaluate research treatment outcome.
4) A research treatment (whether randomly assigned or not) which may be more
costly that a standard treatment.
5) Other substantial costs associated with extra visits to TMC.
GUIDELINES ON COMPENSATION FOR RESEARCH SUBJECTS
COMPENSATION FOR PARTICIPATION (ICMR Code 2000)
Subjects may be paid for the inconvenience and time spent, and should be reimbursed for
expenses incurred, in connection with their participation in research. They may also receive free
medical services. However, payments should not be so large or the medical services so
extensive as to induce prospective subjects to consent to participate in research against their
better judgement (inducement). All payments, reimbursement and medical services to be
provided to research subjects should be approved by the HEC.
Care should be taken:
1) when a guardian is asked to give consent on behalf of an incompetent person, no
remuneration should be offered except a refund of out of pocket expenses;
2) when a subject is withdrawn from research for medical reasons related to the study the
subject should get the benefit for full participation;
3) when a subject withdraws for any other reasons he/she should be compensated in
proportion to the amount of participation.
Prospective participants in research should also be informed of the sponsorship of research, so
that they can be aware of the potential for conflicts of interest and commercial aspects of the
During the initial review of a research protocol, the HEC is required to review both the amount of
compensation proposed and the method and timing of disbursement to assure that neither are
coercive or present undue influence. The following are some additional guidelines:
1) Any compensation should not be contingent upon the subject completing the study, but
should accrue as the study progresses.
2) Unless it creates undue inconvenience or a coercive practice, compensation to subjects who
withdraw from the study should be made at the time they would have completed the study,
had they not withdrawn.
3) Compensation given as a “bonus” or incentive for completing the study is acceptable,
providing that the amount is not coercive. The HEC is responsible for determining if the
incentive amount is not so large as to be coercive or represent undue influence.
4) The amount of compensation should be clearly set forth in the informed consent document.
Reference: ICMR Code 2000
POLICY ON THE USE OF THIRD PARTY/SURROGATE CONSENT
IN RESEARCH AT TMC
When a TMC investigator proposes to conduct a research project utilizing adult subjects who by
virtue of age, physical impairment, mental impairment, language barrier or any other reason
may not be able to personally execute legally effective informed consent, the HEC shall review
the project on the basis of "risk" and "benefit" and shall determine that each project be assigned
to one of the categories below. This policy does not mean to imply that the requirement for
written documentation of consent is waived. Rather, it applies to those studies in which
third party/surrogate consent is obtained from a legally authorized representative.
Investigators must complete and submit an HEC Form for review and approval of inclusion of
subjects who are decisionally impaired.
Category I - Risks to subjects are minimal, direct benefits may or will accrue to subjects.
Category II - Risks to subjects are minimal, direct benefits will not, or are unlikely, to accrue to
subjects but potential societal benefits are inherent in research.
Category III - Risks to subject are greater than minimal, direct benefits may or will accrue to
Category IV - Risks to subjects are greater than minimal, direct benefits will not, or are unlikely,
to accrue to subjects but potential societal benefits are inherent in the research.
EC RECOMMENDATIONS TO THE ADMINISTRATION
When categorization has been accomplished, the HEC will recommend to the TMC
Administration to consider implementation or non-implementation of the project based upon the
level of benefit to be gained by the individual or society from this project as compared to the
level of risk involved.
It is the intent of the HEC to cause to recommend Category I projects to be initiated.
It is the intent of the HEC not to recommend initiation of any Category IV projects.
POLICY ON BLOOD WITHDRAWAL FOR RESEARCH PURPOSES
For many studies where the only research intervention is the collection of blood for analysis, the
HEC categorizes the following procedures for obtaining blood from children and adults as
A. General Requirements
1) There are no special health reasons (e.g., anemia) to contraindicate blood withdrawal.
2) In patients from whom blood is already being drawn for clinical purposes, there are no
other health reasons to preclude additional blood collection.
3) In subjects from whom blood is not already being drawn for clinical purposes, the
withdrawal method is by cutaneous sticks (e.g., heel or finger) or by standard
venipuncture in a reasonably accessible peripheral vein, and the frequency of
punctures does not exceed two per week.
4) The volume of blood drawn from lactating or known pregnant subjects does not exceed
20 ml per week.
5) All blood withdrawals and collections are carried out by experienced professional or
B. Additional Requirements for Adults (Subjects over 18 years of age)
1) If less than 50 ml is being collected, there are no additional restrictions with regard to
hemoglobin or hematocrit.
2) If a volume greater than 50 but less than 200 ml is being collected for “no-benefit”
studies, hemoglobin levels should be >11.0 g/dl for males and >9.5 g/dl for females
with MCVs >85 fl (These restrictions would not apply if iron deficiency anemia or other
forms of anemia were critical for inclusion in the study.).
3) The cumulative volume withdrawn or collected may not exceed 450 ml per twelve-week
period (this maximum includes blood being drawn for clinical purposes) from patients
18 years of age or older in good health and not pregnant.
C. Additional Requirements for Children (Subjects under 18 years of age
1) No more than three (3) skin punctures are to be made in any single attempt to draw
blood, and the frequency of punctures does not exceed twice per week.
2) The volume of blood withdrawn, including blood for clinical purposes, does not exceed
the lesser of 50 ml or 3 ml/kg in an eight week period and collection may not occur
more frequently than 2 times per week.
3) The cumulative volume of clinical and research blood withdrawn per eight-week period
does not exceed six per cent (6.0%) of the child's total blood volume.
4) In patients from whom blood is already being drawn for clinical purposes and when the
research is directly related to the child's condition, there is no maximum number of
extra volume specimens which can be collected as long as the preceding requirements
5) In subjects from whom blood is not already being drawn for clinical purposes, the
maximum number of allowable separate specimens (again, within the limits of the
preceding restrictions) depends upon the child's age and whether the research is
directly related to the child's condition.
D. Cord Blood
Cord blood from newborns can be used without restrictions when blood is extracted from
the placental side of the cord after it has been clamped and severed.
Oral consent is generally sufficient to collect additional volume (within the limits specified
above for minimal risk) from patients in whom blood is being drawn for clinical purposes.
POLICY FOR REVIEW OF HUMAN RESEARCH
INVOLVING INVESTIGATIONAL DRUGS
Research on investigational drugs or DCGI/RA-approved drugs being used in non-approved
ways, or for non-approved populations (e.g., children) must be reviewed by the HEC. If the
investigational drug is DCGI/RA-approved and is to be used in a non-approved fashion or with a
non-approved population, the HEC may require that the investigator obtain approval from the
DGCI/RA. The investigator must supply the approval before the research can be commenced.
Following approval by the HEC, the HEC office will send a copy of the approval letter to the
Dispensary Department. The investigator should supply the Dispensary with a copy of the
research protocol as well as the investigational use material generated by the drug company
prior to starting the study.
The Department of Medical Oncology/PI will be responsible for the storage, and dispensing of
the drugs used in oncology protocols. The drugs should be physically located in the TMH
Dispensary. It will be the responsibility of the PIs in the Adult and Pediatric Oncology groups to
insure that patients receiving these drugs have signed the appropriate consent forms and that
the patient record contains an investigational drug information sheet containing a brief
description of the drug action, possible side effects, dosage and phone number of the
IND APPLICATION EXEMPTION CHECKLIST
This checklist is intended to be used by the investigator as a preliminary test of whether an IND
application needs to be submitted to the DCGI for studies involving DCGI/RA-approved drugs.
If any question is answered "yes", an IND application must be submitted to the DCGI. If the
answers to all questions are "no", then the study may meet the criteria for an exemption from an
1. Name of drug
2. Does the study involve a different route of administration of the marketed drug than
already approved? YES NO
3. Does the study involve the administration of different drug dosage levels that
significantly increase risk or decrease the acceptability of risk to study subjects?
4. Does the study involve the administration of the drug to a different patient population for
whom there may be increased risk or decreased acceptability of risk?
5. Does the study entail any other factor that significantly increases the risk or decreases
the acceptability of risk to study subjects? YES NO
6. Are the results of the study intended to be reported to the DCGI/RA in support of any
significant change in labeling or advertising for the drug (only for corporate sponsored
studies)? YES NO
Signature of Investigator Date
PROCEDURES FOR FILING A NOTICE OF CLAIMED
INVESTIGATIONAL EXEMPTION FOR A NEW DRUG
1. Before a new drug may be tested on human subjects, the sponsor (usually a
pharmaceutical firm or possibly a physician) must give the DCGI/RA the
information specified as a "Notice of Claimed Investigational Exemption for a
New Drug" (IND)
B. REQUIREMENTS FOR THE IND
1. Complete composition of the drug, its source, and manufacturing data to insure
2. Results of all pre-clinical investigations including animal studies. These data
must demonstrate that there will be no unreasonable hazard in using the drug
with humans. Further animal studies may be conducted concurrently with the
3. A detailed outline (protocol) of the planned investigation.
4. Information regarding the training and experience of the investigators.
5. Copies of all informational material supplied to each investigator.
6. An agreement from the sponsor to notify the DCGI/RA and all investigators if any
adverse effects arise during either the animal or human tests.
7. The investigators agreement to obtain the consent of the person on whom the
drug is to be tested prior to the testing.
8. Agreement to submit annual progress reports and commitments regarding
disposal of the drug when studies are discontinued.
C. PHASES OF INVESTIGATIONAL DRUG TESTING
1. Phase I Studies are designed to determine the toxicity, metabolism absorption
and elimination, pharmacological actions, preferred route of administration and
safe dosage range. These studies generally involve a small number of subjects
and are conducted under the careful direction of people trained in Medical
2. Phase II Studies are clinical trials on a limited number of patients for a specific
disease treatment or prevention. Additional pharmacological studies on
animals may be performed concurrently in order to indicate safety.
3. Phase III Studies are in order if the information obtained for Phase I and II
studies demonstrate reasonable assurance of safety and effectiveness, or
suggests that the drug may have a potential value that outweighs its possible
hazards. Phase III studies are intended to assess the drug's safety, specific
disease in a large group of subjects.
D. INVESTIGATOR QUALIFICATIONS
The following information is generally required about the clinical investigator:
1. Education, training and experience.
2. Information about the hospital or medical institution where the study will be
E. OBLIGATIONS OF INVESTIGATORS
1. The investigator must keep careful records of his study and retain them for at
least two years after IND approval.
2. The records must be made available to the sponsor and the DCGI/RA when
3. Regular progress reports must be sent to the sponsor.
4. Reports of adverse reactions must be sent to the sponsor immediately.
5. The investigator must observe the regulations regarding consent of human
subjects involved in research.
GUIDELINES AND POLICY ON INFORMED CONSENT
A GENERAL REQUIREMENTS
Except as described below, investigators may not enroll human subjects in research
unless they have obtained the legally effective, written, informed consent of the subject
or the subject’s legally authorized representative, prior to enrollment of the subject in the
research. Investigators are responsible for insuring that subjects, or their
representatives, are given sufficient opportunity to consider whether or not to participate
and must seek to avoid coercion or undue influence. Information given to potential
subjects or their representatives must be in language that is understandable to the
subject or representative. No process of obtaining consent may include language
through which the subject waives any of their legal rights or releases or appears to
release the investigator, sponsor, or institution or its agents from liability for negligence.
B ELEMENTS OF INFORMED CONSENT
A current sample informed consent document with required phraseology may be found
in Appendix B-2. The sample consent form contains all the required elements of
consent. The HEC requires that all consent forms be written in the first person, e.g., “I
understand that…”. The following are the basic required elements:
1) A statement that the study involves research, an explanation of the purpose of the
proposed research, the duration of the subject’s participation, a description of the
procedures, and which procedures are experimental;
2) The number of subjects that will be involved with the study, totally and at TMC;
3) A description of reasonably foreseeable risks or discomforts that the subjects may
encounter, and, if appropriate, a statement that some risks are currently
4) A description of possible benefits, if any, to the subject and others which may be
reasonably expected. It should be stated that since it is an experimental treatment or
procedure, no benefits can be guaranteed;
5) A discussion of possible alternative procedures or treatments, if any, which are
available to the subject. One alternative might be to choose not to participate in the
research and this will not affect the usual standard of care;
6) A discussion of how confidentiality of records associated with the subject will be
7) A description of any compensation or reimbursement for time, inconvenience, travel,
parking, and other similar costs to the subject;
8) A description of any provisions for treatment of or compensation for research related
9) A statement of whom to contact for answers about the research and in the event
there is a research related injury. (This is generally the PI or another staff member
closely associated with the study.) A separate contact must be named for questions
concerning the subject’s rights;
10) A statement that the subjects’ participation is voluntary, that refusal to participate will
not involve penalty or loss of benefits to which the subject is entitled, and that the
subject may discontinue participation at any time without penalty or loss of benefits;
11) If appropriate, any circumstances under which the subjects participation may be
terminated, with or without the subjects consent; and
12) A description of additional costs for which the subject will be responsible, that are
likely to result from participation in the research study.
C WAIVER OF INFORMED CONSENT
The HEC may waive the requirements for obtaining informed consent or approve a
consent procedure which does not include, or which alters, some or all of the elements
of informed consent listed above, provided that:
1) The research involves no more than minimal risk to the subjects
2) The waiver or alteration will not adversely effect the rights and welfare of the
3) The research could not practicably be carried out without the waiver or alteration;
4) Whenever appropriate, the subjects will be provided with additional pertinent
information after participation.
D DOCUMENTATION OF INFORMED CONSENT
Informed consent must be documented by the use of a written consent form reviewed
and approved by the HEC and signed by the subject or subject’s legally authorized
representative. A copy must be given to the subject or person signing the form. For
TMC patients, a copy of the signed consent form should also be placed in the subject’s
medical record. It is assumed that the consent form is only part of the total consent
process in which the investigator, perhaps using the written consent form as an outline,
describes all facets of the study and answers the subject’s questions. The investigator
is responsible for insuring that research subjects understand the research
procedures and risks. Failure of the subjects to ask questions should not be
construed as understanding on the part of the subject.
E RECORD RETENTION REQUIREMENTS FOR SUBJECT CONSENT FORMS
1) The principal investigator or project director shall maintain, in a designated location, all
executed subject consents. These consent forms are to be available for inspection by
authorized officials of the HEC, DSMSC, regulatory agencies and sponsors. For
DGCI/RA regulated test article studies, all signed subject consent forms shall be
retained by the principal investigator for the appropriate period(s) specified below.
Drugs: Two (2) years following the date a marketing application is approved or the
study is discontinued.
Devices: Two (2) years after a study is terminated or completed and the records are
needed to support DCGI/ RA approval.
POLICY FOR DOCUMENTATION OF INFORMED CONSENT
I. INFORMED CONSENT PROCESS
1. Informed Consent of Subject : For all biomedical research involving human subjects, the
investigator must obtain the informed consent of the prospective subject or in the case of an
individual who is not capable of giving informed consent, the consent of a legal guardian.
Informed consent is based on the principle that competent individuals are entitled to choose
freely whether to participate in research or not. Informed consent protects the individual’s
freedom of choice and respect for individual’s autonomy.
When research design involves not more than minimal risk (for example, where the research
involves only collecting data from subject’s records) the HEC may waive off some of the
elements of informed consent.
Waiver of informed consent could also be considered during conditions of emergency. However,
this would be permissible only if HEC has already approved the study or use of drug. However,
the patient or the legal guardian should be informed after she/he regains consciousness or is
able to understand the study.
2. Obligations of investigators regarding informed consent : The investigator has the duty
i. Communicate to prospective subjects all the information necessary for informed consent.
There should not be any restriction on subject’s right to ask any questions related to the study
as any restriction on this undermines the validity of informed consent.
ii. Exclude the possibility of unjustified deception, undue influence and intimidation. Deception of
the subject is not permissible. However, sometimes information can be withheld till the
completion of study, if such information would jeopardize the validity of research.
iii. Seek consent only after the prospective subject is adequately informed. Investigator should
not give any unjustifiable assurances to prospective subject, which may influence the subject’s
decision to participate in the study.
iv. As a general rule obtain from each prospective subject a signed form as an evidence of
informed consent (written informed consent) preferably witnessed by a person not related to the
trial, and in case of incompetence to do so, a legal guardian or other duly authorised
v. Renew the informed consent of each subject, if there are material changes in the conditions
or procedures of the research or new information becomes available during the ongoing trial.
vi. Not use intimidation in any form which invalidates informed consent. The
investigator must assure prospective subjects that their decision to participate or
not will not affect the patient - clinician relationship or any other benefits to
which they are entitled.
3. Essential information for prospective research subjects: Before requesting an
individual’s consent to participate in research, the investigator must provide the individual with
the following information in the language he or she is able to understand which should not only
be scientifically accurate but should also be sensitive to their social and cultural context :
i. the aims and methods of the research;
ii. the expected duration of the subject participation;
iii. the benefits that might reasonably be expected as an outcome of research to the
subject or to others;
iv. any alternative procedures or courses of treatment that might be as advantageous to
the subject as the procedure or treatment to which she / he is being subjected;
v. any foreseeable risk or discomfort to the subject resulting from participation in the
vi. right to prevent use of his / her biological sample (DNA, cell-line, etc.) at any time
during the conduct of the research;
vii. the extent to which confidentiality of records could be maintained ie., the limits to
which the investigator would be able to safeguard confidentiality and the anticipated
consequences of breach of confidentiality;
viii. responsibility of investigators;
ix. free treatment for research related injury by the investigator / institution;
x. compensation of subjects for disability or death resulting from such injury;
xi. freedom of individual / family to participate and to withdraw from research any
time without penalty or loss of benefits which the subject would otherwise be entitled to;
xii. the identity of the research teams and contact persons with address and phone
xiii. foreseeable extent of information on possible current and future uses of the
biological material and of the data to be generated from the research and if the material
is likely to be used for secondary purposes or would be shared with others, clear
mention of the same;
xiv. risk of discovery of biologically sensitive information;
xv. publication, if any, including photographs and pedigree charts.
The quality of the consent of certain social groups requires careful consideration as their
agreement to volunteer may be unduly influenced by the Investigator.
This is accomplished as part of the total consent process by using a consent form that has been
reviewed and approved by the HEC. Confusion sometimes arises as to who can obtain consent
and who can be designated to sign the consent form. The following are the acceptable methods
for documentation of informed consent of human research subjects at TMC:
1. The HEC must be made aware of the person (s) who will be conducting the consent
interviews. These faculty/staff members should be the only personnel allowed to
obtain consent unless indicated otherwise. The HEC requires that the person
obtaining consent is medically trained.
2. Each subject (or their legally authorized representative) must be provided adequate
time to read and review the consent form, in addition to being advised of the
procedures, risks, potential benefit, alternatives to participation, etc. This is
frequently accomplished using the consent form as an outline for the interview
3. After completing the consent interview and assuring that the subject (or their
representative) has no further questions and agrees to participate in the research
activity, the interviewer should instruct the subject to sign and date the consent form
in the appropriate spaces.
4. A witness must sign and date in the appropriate spaces. The witness cannot be the
person conducting the consent interview, but is not further restricted.
5. The person conducting the consent interview must then sign and date the consent
form in the appropriate spaces (PI or designee). It is assumed that in most cases, all
persons signing the consent form will do so at the conclusion of the consent
6. Each subject (or their representative) must be given a copy of the signed consent
form. The original consent form should be filed in such a manner as to insure
immediate retrieval when required by auditing entities, HEC, or sponsor monitors.
7. The regulations are clear that written documentation informed consent is required.
Therefore, obtaining consent from an authorized third party via the telephone is not
8. The regulations also include provisions for approval of a waiver or alteration of part
or all of the consent process. The HEC will consider written requests for waiver or
alteration of the process when accompanied by sufficient justification.
9. Obtaining informed consent from subjects must be accomplished prior to performing
the research activity and using only an HEC approved consent form. Written
requests for amendments to an existing consent form must be approved by the HEC
prior to implementation.
10. Upon receipt of an HEC approved consent form, all old versions should be
discarded to prevent inadvertent use of an outdated consent form. Copies of the
most recently approved consent form may be made and should be used until
superceded by an amended consent form. The consent form must be reviewed at
least annually as part of the continuing review process.
POLICY ON REPORTING SERIOUS ADVERSE EVENTS AT TATA MEMORIAL CENTRE
When a person who is participating in research protocol experiences a serious adverse reaction,
the principal investigator is required to report the incident to the HEC.
If the adverse events were anticipated as a part of the protocol and the research subject was
informed in the consent form, the HEC does not need to be notified unless the adverse event was
unexpectedly serious, life threatening or fatal.
If the adverse events were unanticipated, required that the subject be hospitalized or death has
occurred, the adverse event(s) must be reported to the HEC within 24 hours.
If the research project is being supported with funds from outside the institution, the investigator is
responsible also for notifying the sponsor. The sponsor may also be required to notify the
DCGI/RA or other government agencies within 24 hours of the occurrence of the adverse event(s).
If the faculty member holds an Investigational New Drug (IND) or Investigational Device Exemption
(IDE) in his/her name, he/she is required to notify the DGCI/RA within 24 hours of any
unanticipated adverse reactions in addition to notifying the HEC.
Notifying the HEC does not relieve the investigator from his/her responsibility to notify the sponsor,
Within 24 hours of learning about an adverse event, the principal investigator is responsible for
notifying the HEC Office. The investigator is to submit a written report to the HEC within 10
EXAMPLES OF CATEGORIES OF RESEARCH THAT MAY BE REVIEWED BY THE HEC
THROUGH AN EXPEDITED REVIEW PROCEDURE
An expedited review procedure consists of a review of research involving human subjects by the
HEC chairperson or by one or more experienced reviewers designated by the chairperson from
among members of the HEC.
A Research activities that
1present no more than minimal risk to human subjects, and
2involve only procedures listed in one or more of the following categories, may be
reviewed by the HEC through the expedited review procedure. The activities listed should
not be deemed to be of minimal risk simply because they are included on this list.
Inclusion on this list merely means that the activity is eligible for review through the
expedited review procedure when the specific circumstances of the proposed research
involve no more than minimal risk to human subjects.
B The categories in this list apply regardless of the age of subjects, except as noted.
C The expedited review procedure may not be used where 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.
D The standard requirements for informed consent (or its waiver, alteration, or exception)
apply regardless of the type of review, expedited or convened, utilized by the HEC.
E Categories one (1) through seven (7) pertain to both initial and continuing HEC review.
1Clinical studies of drugs and medical devices only when condition a or b is met.
a Research on drugs for which an investigational new drug application is not
required. (Note: Research on marketed drugs that significantly increases the risks or
decreases the acceptability of the risks associated with the use of the product is not
eligible for expedited review.)
b Research on medical devices for which
iian investigational device exemption application is not required; or
iiithe medical device is cleared or approved for marketing and the medical
device is being used in accordance with its cleared/approved labeling.
2Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as
afrom healthy, non-pregnant adults who weigh at least 110 pounds. 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
b from other adults and children, 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 the lesser of 50 ml or 3 ml per kg in an 8 week period and collection may not
occur more frequently than 2 times per week.
3 Prospective collection of biological specimens for research purposes by noninvasive
a hair and nail clippings in a non-disfiguring 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 unstipulated 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
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
j sputum collected after saline mist nebulization.
4 Collection of data through noninvasive procedures (not involving general anesthesia
or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or
microwaves. Where medical devices are employed, they must be cleared/approved for
marketing. (Studies intended to evaluate the safety and effectiveness of the medical device are
not generally eligible for expedited review, including studies of cleared medical devices for new
a physical sensors that are applied either to the surface of the body or at a
distance and do not involve input of significant amounts of energy into the subject
or an invasion of the subject's privacy;
b weighing or testing sensory acuity;
c magnetic resonance imaging;
d electrocardiography, electroencephalography, thermography, detection of
naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging,
doppler blood flow, and echocardiography;
e moderate exercise, muscular strength testing, body composition assessment,
and flexibility testing where appropriate given the age, weight, and health of the individual.
5 Research involving materials (data, documents, records, or specimens) that have
been collected or will be collected solely for non-research purposes (such as medical treatment
6 Collection of data from voice, video, digital, or image recordings made for research
7 Research on individual or group characteristics or behavior (including, but not
limited to, research on perception, cognition, motivation, identity, language,
communication, cultural beliefs or practices, and social behavior) or research
employing survey, interview, oral history, focus group, program evaluation, human
factors evaluation, or quality assurance methodologies.
8 Continuing review of research previously approved by the convened HEC as
A where (i) the research is permanently closed to the enrollment of new
subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research
remains active only for long-term follow-up of subjects; or
B where no subjects have been enrolled and no additional risks have been
C where the remaining research activities are limited to data analysis.
9 Continuing review of research, not conducted under an investigational new drug
application or investigational device exemption where categories two (2) through eight
(8) do not apply but the HEC has determined and documented at a convened meeting
that the research involves no greater than minimal risk and no additional risks have
HEALTH RECORD RESEARCH
The following is the HEC policy concerning research involving the study of medical
records or other forms of health information.
Research projects may involve the study of Patient case files with the stipulations
described below. Such studies raise issues of confidentiality that must be carefully addressed
by the investigator and the official custodian of the records. If it is anticipated that an
individual's records or specimens will likely be used for research purposes, the potential subject
should be informed of the potential use of such materials upon entry into the institution or
program in which the materials will be developed or collected and be given an opportunity to
either provide or refuse consent to such research. Patient case files may always be used or
disclosed for research purposes if it has been de-identified and linkage back to a specific patient
would not be possible.
To use or disclose identifiable Patient case files without authorization of the research
participant, the investigator must accomplish one of the following:
1) complete and submit an HEC Form to request waiver of the requirements for
obtaining informed consent;
2) provide written documentation that the use of disclosure of patient case files is solely
used to design a research protocol or to assess feasibility of conducting a study, or;
3) document that the use or disclosure is solely for research on the patient case files of
Investigators must maintain in their files a letter from the HEC identifying the date on
which the waiver or alteration of the requirements to obtain informed consent was approved by
the HEC, and a statement that the HEC has determined that the waiver or alteration satisfies
the following criteria:
1) The use or disclosure of patient case files involves no more than minimal risk to the
2) The alteration or waiver will not adversely affect the privacy rights and welfare of the
3) The research cannot practicably be conducted without the alteration or waiver;
4) The research could not practicably be conducted without access to or the use of the
patient case files;
5) The privacy risks to individuals whose Patient case files is to be used or disclosed are
reasonable in relation to the anticipated benefits, if any, to the individuals, and the
importance of the knowledge that may reasonable be expected to result from the
6) There is an adequate plan to protect the identifiers from improper use and disclosure;
7) There is an adequate plan to destroy the identifiers at the earliest possible opportunity
consistent with the conduct of the research, unless there is a health or research
justification for retaining the identifiers, and;
8) There are adequate written assurances that the Patient case files will not be reused or
disclosed to any other person or entity, except as required by law, for authorized
oversight of the research project, or for other research for which the use or disclosure
of Patient case files would be permitted by this policy.
The HEC letter should also contain a brief description of the Patient case files for which
use or access has been determined by the HEC to be necessary, a statement that the waiver or
alteration was approved by Expedited Review or at a convened meeting, and the letter should
be signed by the HEC Chair or the Chair’s designee.
Research use or disclosure of identifiable Patient case files with authorization of the
research participant is permitted providing that use or disclosure is for only the Patient case files
that was originally authorized. In order to use or disclose additional information, the investigator
would either have to obtain consent or request a waiver of the requirements to obtain consent.
GUIDELINES FOR RESEARCH PROTOCOLS WHICH REQUIRE
COLLECTION AND STORAGE OF GENETICS MATERIALS
For the purpose of these guidelines, "Genetic Materials" are defined as human tissue samples
(blood, serum, tumor, etc.) on which genetic related research, such as biochemical studies of
inherited human traits or identification of DNA mutations, may be performed.
A. Previously acquired samples
1. Previously acquired genetic material may be used if identifiers are stripped irrevocably
2. If identifiers are present, experiments not described in present protocols must be
submitted for HEC review.
B. Prospectively acquired samples
1. Anonymous samples (further identification made impossible)
a) Ownership of genetic material will generally remain with the institution. This must be
stated in the consent form.
b) The general scope of the investigations must be explained in the consent form, but
new avenues of investigation in the future are permissible if this possibility is explained
in the consent form.
c) Whether the genetic material will be shared by other investigators should be explicit in
the consent form.
d) The consent form should make clear that no specific information relative to the
individual donor will be forthcoming; however, information that accrues from the study
that is valuable to society may be shared with the individual.
2. Identified samples
a) If genetic material is linked to the donor by specific identifiers, ownership of the
material will generally remain with the institution. If a commercial use is anticipated for
the genetic material, the individual must be notified. The general policy of ownership
should be stated in the consent form using the following wording:
"I understand that additional or "leftover" (blood, serum, tumor, etc.) tissue may be used
for future research which may result in financial gain for TMC and the researchers. I
also understand that my donated tissue will be one of many that are used in the
research and it will be virtually impossible to attribute findings to any one sample. I
understand, however, that I am not otherwise waiving any of my legal rights by
participating in this study."
b) If identifiers are present, new experiments must be reviewed by the EC and new
consent obtained from the research participant regardless of the details of ownership.
c) The investigator may include a provision in the consent form for new experiments not
requiring new consent if identifiers are irrevocably removed from the samples. If the
investigator anticipates future experiments without identifiers, this possibility should be
present in the original consent form. The methods for removal of identifiers must be
approved by the EC. Removal of identifiers must not be employed as a method of
avoiding ownership issues.
d) A satisfactory method for sharing or withholding information gained by the research
must be in the research protocol and clearly indicated in the consent form.
e) Details for sharing or not sharing the genetic material with other investigators must be
present in the protocol and clearly indicated in the consent form.
f) The length of time the genetic material will be maintained must be indicated in the
C. Donation of genetic material as a requirement for participation in a research protocol.
1. Donation of genetic material may be required for participation in a protocol only if the
presence of the genetic material is necessary to satisfy the central question of the research.
2. The investigator will be required to make a clear case in the research protocol for the
necessity of the genetic material, if donation of genetic material is mandatory.
3. This policy applies to genetic material with or without identifiers.
GUIDELINES FOR SUBMISSION AND EC REVIEW OF GENE THERAPY/GENE TRANSFER
As of October 10, 2000 the ICMR formulated Ethical Guidelines for Biomedical Research on
Human Subjects. ICMRs goal is to insure that no research participant is enrolled in a human
gene therapy/gene transfer research protocol before the local HEC have the benefit of the broad
perspective and experience in protocol review and risk assessment.
In November 2001, the Department of Biotechnology also finalised the Ethical Policies on the
Human Genome, Genetic Research and Services.
Guidelines are available at the Office of Biotechnology Activities Internet site
The following items are required to be addressed in the protocol to provide the necessary
information for EC review:
A Background and justification
• Why is this disease a good candidate for gene transfer or gene therapy?
• What previous work has been done, including studies of animals and cultured cell models?
Does the work demonstrate effective gene delivery? How does the proposed study relate to
• Is the disease course sufficiently predictable to allow for meaningful assessment of the
results of the treatment proposed?
• What level of gene expression is presumed to be required to achieve the desired effect?
• Given responses to the above questions, is there a sufficient justification for the investigator
to proceed at this point to a clinical trial?
B Research design
• What are the objectives of the proposed study (e.g., establishing feasibility or relative safety
of the gene transfer, determining therapeutic effectiveness, establishing a safe dose range,
demonstrating proof of principle, etc.)?
• Is the goal of the study to ameliorate or cure disease or to enhance healthy individuals?
• What is the target tissue for gene transfer (e.g., bone marrow cells, skeletal muscle cells,
respiratory epithelial cells, central nervous system tissue, etc.)?
• What method(s) (e.g., direct injection, inhalation, ex vivo genetic modification with injection
of modified cells) and reagent(s) (e.g., vectors based on retroviruses, adenoviruses, adeno-
associated viruses, herpes viruses) will be employed for gene delivery? What is the
rationale for their use? Are other methods or reagents known that are more appropriate with
regard to efficacy, safety, and stability?
• How will the investigator determine the proportion of cells that acquires and expresses the
• How will the investigator determine if the product is biologically active?
• Is the planned statistical treatment appropriate: i.e., is it likely to provide valid answers to
the study question?
• Is it reasonable to expect that the research design proposed will meet the investigator’s
• What research-specific procedures and research-specific investigations are required by the
study over and above those that would be required for patients receiving standard clinical
care (e.g., physical examinations, venous or arterial blood tests, collection of target cells,
imaging procedures, irradiation, chemotherapy, direct injection of vector, re-injection of
genetically modified cells, organ or tissue transplantation, surgery, tissue/tumor donation,
• Is long term follow-up appropriate or essential for this protocol? If long term follow-up is
proposed, is there justification for the number of visits and the length of time required? Is
such follow-up feasible in the case of this protocol (e.g., have provisions been made for
subjects who move? Is adequate funding available for such follow-up?)?
• What are the procedures for obtaining or maintaining information in a data/DNA bank (e.g.,
use of identifiers, limitation on access, need for consent, sharing with other investigators,
duration of storage, future subject contact)?
• Are all of the research-specific procedures necessary? In combination with data collected in
the course of clinical care, is it reasonable to expect that the information produced by this
study will be sufficient to answer the research question?
• Are the practical steps for maintaining confidentiality of data/records/database information
clearly specified and adequate (e.g., encryption, use of unique identifiers, sequestering of
records, security measures)?
E Subject selection
• How has the study population been defined?
• Has an adequate rationale been provided for each eligibility criterion (e.g., safety
considerations, definition of disease, avoidance of additional concurrent therapies,
administrative considerations)? Do they strike a defensible balance between scientific
validity and generalizability (i.e., is the study population sufficiently, but not unduly, restricted
so as to yield interpretable results)?
• How will subjects be recruited? If a cohort of eligible patients exists, how will selection be
made amongst them? If several trials exist for which the same patients are eligible, how will
this be presented to prospective subjects?
• Does the definition of the research population reflect appropriate scientific, clinical, and
ethical norms? In recruiting and negotiating with potential subjects, have the norms of
nondiscrimination been respected?
F Risks, discomforts, and benefits
• What risks and discomforts are associated with the research-specific procedures and
investigations (e.g., surgery, chemotherapy, radiation, bone marrow transplantation)? Have
they been minimized?
• If a virus-mediated gene transfer is proposed, what is the potential for the presence of a
replication-competent or pathological virus or other form of contaminants? How sensitive
are the tests to detect such viruses or contaminants? What level of viral presence or other
form of contamination would be tolerable in this protocol?
• Has the possibility of vertical transmission (i.e., gene insertion into germ cells or a fetus) or
horizontal transmission (e.g., to family members or health care staff) been considered?
What measures have been taken to minimize the risks of transmission? Are other
measures possible? If transmission were to occur, what would be the consequences?
• What are the risks for the vector to activate an oncogene or inactivate a tumor suppressor
gene leading to vector-related malignancy?
• Are the risks and discomforts of the study justified given the potential benefit to subjects and
the scientific importance of the research?
F Information to subjects
• Have prospective participants been adequately informed of the following:
1. What is being studied and why, giving details about study procedures, known or
potential risks, discomforts and benefits, and alternatives to participation;
2. Their rights: (a) to information on an ongoing basis, confidentiality with regard to their
participation and handling of their data, and the right to consult with others before
making a decision whether to participate; and (b) to withdraw from the study without
penalty or loss of benefits, as well as of any health consequences of withdrawal for
themselves or their immediate contacts, or limitations on withdrawal, if any;
3. Any special issues related to this gene therapy trial, such as uncertainty associated with
short and long term risks and benefits or the possibility of media attention; and
4. Any commercial or financial interests in the research.
• Have prospective participants been provided this information in simple language, using
translation where necessary, with answers to their questions, referral to other sources of
information, and adequate time to make up their minds whether to participate?
• If there is no individual benefit from participation in the research, has this been appropriately
• Will the general study results be made available to subjects?
• Do all of the elements of the consent process combine to allow subjects a full opportunity to
make an informed choice?
1. Reference: Ethical Guidelines for Biomedical Research on Human Subjects ICMR 2000
HEC POLICY FOR DATA AND SAFETY MONITORING IN CLINICAL RESEARCH
Concerns for assuring the safety and welfare of subjects participating in clinical research studies
have prompted the issuance of guidance and policies on oversight of clinical trials. More
specifically, investigators are now required to establish plans for ongoing, real time data and
safety monitoring. Specific responsibility for and methods of data and safety monitoring depend
on the sponsor of the study and the phase of the study. The methods and amount of monitoring
required are somewhat dictated by the degree of risk involved to the individual subjects and the
complexity of the clinical research. Some clinical research activities may require the
establishment of a Data and Safety Monitoring Board/Committee to review interim analyses of
data and cumulative toxicity data to determine if the research activities should continue as
originally designed, be changed, or be terminated.
The following policy describes the parties responsible for data and safety monitoring and the
acceptable methods of conducting the monitoring.
For these types of studies, it is the responsibility of the sponsor (person or persons initiating the
clinical trial) to notify the DCGI/RA of any serious and/or unexpected adverse event. Most
sponsors establish their own Data and Safety Monitoring Committee (DSMC) to review interim
analysis, toxicity data and adverse events, and recommend a course of action to the sponsor if
it appears that there are unreasonable risks to subject safety. Investigators are required to
promptly report adverse events to the HEC and the sponsor. If review of adverse event reports
from TMC or other sites raises concerns that subject safety and welfare are at increased risk,
the HEC may suspend the study locally even if the sponsor decides to continue with the study.
1. Phase I and II studies may be monitored by the investigator/project manager, or a designee,
or by both. There is no requirement for establishment of a DSMC but there is a requirement
for written policies and procedures that describe the monitoring and reporting processes.
HEC must approve these policies and procedures.
2. Phase III clinical studies must be monitored by a DSMC. If the studies are to be conducted
at multiple sites, the DSMC must be established by the “study leadership” that may or may
not be at TMC. The HEC must be informed of the composition and location of the DSMC in
either case. In addition, a plan for DSMC submission of a periodic summary of adverse
events to the HEC must be in place. This does not relieve the investigator of his/her
responsibility of promptly reporting adverse events that occur at TMC.
Investigator Initiated Clinical Studies
Investigator initiated studies are defined as clinical research activities with a drug or device that
are not supported by or solicited by an industry sponsor, although the study may receive
support from an industry sponsor. The Data and Safety Monitoring Sub Committee of the HEC
will monitor the studies at TMC sites. If they involve multiple sites with a TMC investigator acting
as the “study leadership”, an independent DSMC must be established.
Detailed information of the Data and Safety Monitoring Subcommittee is available in the SOPs
of the DSMSC.
POLICY FOR SUBMISSION OF AUDIT REPORTS
The HEC is responsible for local oversight of all human subject research and for assuring, to the
greatest extent possible, the safety and welfare of the research subjects. To carry out its
responsibilities, the HEC reviews all new proposals, provides continuing review of research
activities, reviews adverse event reports, and, if necessary, undertakes on-site audits of
investigator research records.
Conducting research utilizing human subjects, by regulation and from a practical standpoint, is
based on a system of trust in the integrity of the investigator. Specifically, the HEC trusts that
the investigator will conduct responsible research and keep the safety and welfare of the
subjects in mind at all times. It also assumes that when inadvertent protocol deviations occur,
the investigator will notify the HEC of the deviation and the corrective actions taken to prevent
Oversight of clinical trials may occur by several methods, one of which is the audit process
conducted by a Contract Research Organization (CRO), sponsor monitor etc. The audit
process, often viewed in a negative sense, can also be viewed as a valuable oversight function.
The audits may identify potential issues of concern regarding subject safety and welfare that
can be corrected, thereby preventing injury to a research subject.
It is the policy of the HEC that a copy all reports of audits performed by CROs, sponsor
monitors, or any other external or internal entity is submitted to the HEC/DSMSC promptly upon
receipt of the report from the auditing entity. This policy exists to ensure oversight by the HEC
and appropriate TMC officials so that research subjects may be better protected.
REPORT FORM FOR ADVERSE EVENTS IN HUMAN SUBJECTS
AT TATA MEMORIAL CENTRE
Within 24 hours of learning about an adverse event, the principal investigator is responsible for
notifying the HEC. Within 10 working days the principal investigator is to submit a written report to
the HEC in the following format:
1) The title of the project is:
The principal investigator is:
Summary of subject with the adverse event: Case No. Sex: M F Age:
2) Please provide a succinct description of the adverse events (who, what, where and
when) and attach any other pertinent documentation. (Please indicate if this is a follow-
up report and if so, include follow-up information only.)
3) Describe the specific adverse event and check all that apply.
Anticipated Event Unanticipated Event
Death Hospitalization Significant Disability Other
4) Describe the medical treatment (if any) that was provided to the research subject and the
5) How far into the protocol had the subject progressed before the adverse event occurred?
6) What is the long-term prognosis of the patient and will the patient continue to receive
7) Was the research subject continued on the research protocol? yes no
8) In your opinion, was the adverse event a result of participation in the research protocol?
probably possibly unlikely unknown or not enough information to judge
9) Please provide your estimation of the severity of the event by circling the appropriate
number associated with the descriptions below:
0. No Disability: No significant resultant discomfort; no cosmetic or functional
impairment, and no increased length of stay or significant use of additional resources
as a result of the AE.
1. Minor Temporary: Minimal to moderate clinical effect requiring no or minimal clinical
intervention, or no increased length of stay or re-hospitalization for the same or
2. Minor Permanent: Minimal to moderate clinical effect with permanent residual effect
but without significant functional or cosmetic impairment.
3. Major Temporary: Moderate to severe clinical effect with no significant cosmetic or
functional residual effect. This usually results in increased length of stay or re-
hospitalization and requires moderate to major clinical intervention.
4. Major Permanent: Moderate to severe clinical effect with significant functional or
cosmetic residual effect.
5. Potential Major or Major Continuing: When doubt exists as to the outcome, but the
probability is that major impairment or repeated re-hospitalization will be necessary.
10) a) Was the protocol followed in recruitment of the subject? yes no
b) Did the patient meet the exclusion/inclusion criteria of the protocol? yes no
c) Was informed consent obtained as outlined in the protocol? yes no
If no to any part of question 8, please explain:
11) In your opinion, does this report require that the consent form for subjects be revised?
_____ no_____ yes
If yes, submit two revised consent forms. One with the proposed changes emphasized in
some fashion (highlighter, bolded, etc.) and another clean copy.
Signature of PI Date
Upon receipt of this report, the HEC/DSMSC will decide whether additional information is needed
or whether further investigation of the incident is required.
Do Not Write Below This Line. For HEC Use Only.
I agree disagree with the assessment of the principal investigator.
DSMSC Reviewer Date
SUBJECT CONSENT FORM
SAMPLE CONSENT FORM
Title of Protocol
You are invited to participate in a study of (state what is being studied). We hope to learn (state
what the study is designed to discover or establish).
You were selected as a possible participant in this study because (state why the subject was
Your participation in this study is entirely voluntary.
Your decision whether or not to participate will not prejudice you or your medical care. If you
decide to participate, you are free to withdraw your consent and to discontinue participation at
any time without prejudice to you or effect on your medical care.
If you decide to participate, we (or Dr. _______ and his or her associates) will (describe
procedures to be followed, including their purposes, how long they will take and their frequency).
(Describe the discomforts and inconveniences reasonably to be expected and the amount of
blood to be drawn, if any.) (Describe any reasonably foreseeable risks.) (State the approximate
number of subjects to be enrolled, and the total time subjects will be involved.) (Describe any
benefits that may be reasonably expected.) (After describing the potential benefits, state:)
WE CANNOT AND DO NOT GUARANTEE OR PROMISE THAT YOU WILL RECEIVE ANY
BENEFITS FROM THIS STUDY.
You will be told if any new information is learned which may affect your condition or influence
your willingness to continue participation in this study.
While participating in this study, you should not take part in any other research project without
approval from all of the investigators. This is to protect you from possible injury arising from such
things as extra blood drawing, extra x-rays, interaction of research drugs, or similar hazards.
Describe appropriate alternative procedures, if any, that might be advantageous to the subject.
Any standard treatment that is being withheld must be disclosed. If there is no alternative
treatment state: "the alternative is not to participate".
Any data that may be published in scientific journals will not reveal the identity of the
subjects. Patient information may be provided to Governmental and regulatory agencies as
required. (If applicable, state the persons or agencies to whom the information will be furnished
and the nature of the information to be furnished).
(Please include the amount of payment, if any, and the schedule of payment.) If payment is
made in money or gifts the following statement must be included (verbatim): If the patient will not
be paid please use the following statement- No payment will be provided for participation in this
(Please include information regarding the cost of participating in the study.) The sponsor will
pay for _________. You or your insurance company will be responsible for ________________.
(Disclose what institution(s) or companies are involved in the study through funding,
cooperative research, or by providing study drugs or equipment. The following generic disclosure
is acceptable __________________________________ (Name of institution /company) is
providing financial support and/or material for this study.
(If consultative or financial relationships exist, include the following statement): One or more
of the investigators has a (state whether paid or unpaid) consultative and/or financial relationship
with the sponsoring organization(s) involved in this research.
At the discretion of the protocol director subjects may be taken out of this study due to
Some possible reasons for withdrawing a subject from the study. (Note to investigator: you
may use these reasons and/or add some of your own).
- failure to follow instructions
- the investigator decides that continuation could be harmful to you
- you need treatment not allowed in the study
- the study is canceled
- other administrative reasons
(If this study falls within the jurisdiction of the DCGI, use the following sentences:) 1) The
purpose of this research is to obtain data or information on the safety and effectiveness of (name
of drug, device, etc.); the results will be provided to the sponsor, Drug Controller General of India,
the Food and Drug Administration and other agencies as required. 2) If you think you have
experienced a research related injury call name of doctor at phone number.
If you have any questions, we expect you to ask us. If you have any additional questions later,
(doctor's name) at (doctor's telephone number) will be happy to answer them.
If the study includes MRI (Magnetic Resonance Imaging) include the following:
(Minimal revisions may be made to fit your study)
This MRI machine uses a strong magnet and radio waves to make images of the body interior.
The scanning procedure is very much like an x-ray CT scan. You will be asked to lie on a long
narrow couch for a certain amount of time (state how long) while the machine gathers data.
During this time you will not be exposed to x-rays, but rather a magnetic field and radio waves.
You will not feel either. You will, however, hear repetitive tapping noises that arise from the radio
antenna around your body. We will provide earplugs or ear phones that you will be required to
wear. The space within the large magnet in which you lie is somewhat confined, although we
have taken many steps to relieve the "claustrophobic" feeling.
There are no known significant risks with this procedure at this time because the radio waves and
magnetic fields, at the strengths used, are thought to be without harm. The exception is if you
have a cardiac pacemaker, or a certain type of metallic clip in your body (i.e., an aneurysm clip in
There is a possibility that you will experience a localized twitching sensation due to the magnetic
field changes during the scan. This is not unexpected and should not be painful. However, you
can discontinue the exam at anytime.
The magnetism and radio waves do not cause harmful effects at the levels used in the MRI
machine. National and Stanford guidelines have been developed for these machines, and these
recommendations will be followed. However, because the MR scanner uses a very strong
magnet that will attract metal, all metallic objects must be removed from your person before you
approach the scanner. In addition, watches and credit cards should also be removed as these
could be damaged. (These items will be watched for you).
If you have any history of head or eye injury involving metal fragments, if you have ever worked in
a metal shop, if you have some type of implanted electrical device (such as a cardiac pacemaker)
, if you have severe heart disease (including susceptibility to arrhythmias), if you are wearing
metal braces on your teeth, or ( for women) if you could be pregnant, you should not have an MR
(optional – only if MRI is done in hospital) If you wish, we can prescribe a mild sedative to help
you to relax during the scan session. Because you may still feel sleepy after taking this
medication, you should not plan on driving yourself after the MRI.
NOTE: IF ALL OF THE SEQUENCING TO BE USED HAS NOT BEEN APPROVED BY THE
FOOD AND DRUG ADMINISTRATION, THIS MUST BE STATED IN THE CONSENT FORM.
(The following language is recommended when women of childbearing potential (non-
pregnant) will be enrolled in an investigational drug study.)
WOMEN OF CHILDBEARING POTENTIAL
If you are a woman who is able to become pregnant, it is expected that you will use an effective
method of birth control to prevent exposing a fetus to a potentially dangerous agent with unknown
risk. If you are pregnant or currently breast feeding, you may not participate in this drug study.
You understand that if you are pregnant, if you become pregnant, or if you are breast-feeding
during this study, you or your child may be exposed to an unknown risk [or state specific risk].
To confirm to the extent medically possible that you are not pregnant, you agree [to have a
pregnancy test done before beginning this research study] [to begin the study after the onset of
your next menstrual period] (choose one). You must agree to avoid sexual intercourse or use a
birth control method judged to be effective by the investigator and which will not interfere with the
proposed investigation. You must accept the risk that pregnancy could still result despite the
responsible use of reliable method of birth control. You agree to notify the investigator as soon
as possible of any failure of proper use of your birth control method, or if you become pregnant,
either of which may result in your being withdrawn from the study.
CONSENT FOR TISSUE SAMPLING OR BANKING FOR RESEARCH
Research using tissues is an important way to try to understand human disease and/or the role
genes play in disease. You have been given this consent form because the investigators want
to include your tissues in a research project, or because they want to save such samples for
research. There are several things you should know before allowing your tissues to be studied:
1. You are invited to participate in a study
We hope to learn (state what the study is designed to discover or establish).
You were selected as a possible participant in this study because (state why the subject was
2. Your tissues will be stored [under your name or other unique identifier] (choose one). Your
name or other public identifiers will not be included with any data shared with other
Once the sample is taken, it will forever be separated or unlinked from your name. This will
protect your identity and preserve anonymity. However, once you donate the sample, you
will not be able to withdraw your tissues from the research project because the samples will
not be traceable.
3. There are no risks involved in research on the samples provided by you.
4. You will be told the results of the tests, but not of any other research tests in the future.
You will not be told the results, even if there might be some potential benefit to you.
5. You have the right to refuse to allow your tissues to be studied now or saved for future study.
You may withdraw from this study at any time. The investigators might retain the identified
samples, e.g., as part of your routine clinical care, but not/and for additional research.
6. The investigator will not provide genetic information about you to your familly members, but
you may wish to.
You [ consent / withhold consent ] for the investigator to provide genetic information about
you to your family members.
7. Investigators in this study may try to recontact you in the future. If you are, understand the
Information may be too sketchy to give you particular details or consequences.
You may be determined to carry a gene for a particular disease that can be treated.
You may be determined to carry a gene for a particular disease for which there is no current
8. Any tissues you have donated which are used in research may result in new products, tests
or discoveries. In some instances, these may have potential commercial value and may be
developed and owned by the Investigators, of TMC or others. However, donors of tissues
do not retain any property rights to the materials. Therefore, you would not share in any
financial benefits from these products, tests or discoveries.
Signature of Participant Date
Person Obtaining Consent
I attest that the requirements for informed consent for the medical research project described in
this form have been satisfied. I have discussed the research project with the participant and
explained to him or her in nontechnical terms all of the information contained in this informed
consent form, including any risks and adverse reactions that may reasonably be expected to
occur. I further certify that I encouraged the participant to ask questions and that all questions
asked were answered.
Signature of Person Obtaining Consent Date
Signature of Parent or Guardian Date
(If consent is to be obtained from a parent(s), legal guardian
CONSENT FOR GENE THERAPY STUDIES
(If the protocol involves gene therapy the following two items must be included):
1.) The approximate number of people who have previously received the genetic material under
2.) "To obtain vital information about the safety and efficacy of gene transfer, at the time of death,
no matter what the cause, permission for an autopsy will be requested of your family. Please
advise your family of this request and of its scientific and medical importance".
*All forms of medical diagnosis and treatment -- whether routine or experimental -- involve some
risk of injury. In spite of all precautions, you might develop medical complications from
participating in this study. If such complications arise, the researchers will assist you in obtaining
appropriate medical treatment but this study does not provide financial assistance for additional
medical or other costs. (Additionally TMC is not responsible for research and medical care by
other institutions or personnel participating in this study.) You do not waive any liability rights for
personal injury by signing this form. In addition, if you are not satisfied with the manner in which
this study is being conducted or if you have any questions concerning your rights as a study
participant, please contact the Ethics Committee Tata Memorial Hospital.
*Please add the following Bill of Rights to your consent.
As a human subject you have the following rights. These rights include but are not limited to
the subject's right to:
۰ be informed of the nature and purpose of the experiment;
۰ be given an explanation of the procedures to be followed in the medical
experiment, and any drug or device to be utilized;
۰ be given a description of any attendant discomforts and risks reasonably to be
۰ be given an explanation of any benefits to the subject reasonably to be
expected, if applicable;
۰ be given a disclosure of any appropriate alternatives, drugs or devices that might
be advantageous to the subject, their relative risks and benefits;
۰ be informed of the avenues of medical treatment, if any available to the subject
after the experiment if complications should rise;
۰ be given an opportunity to ask questions concerning the experiment or the
۰ be instructed that consent to participate in the medical experiment may be
withdrawn at any time and the subject may discontinue participation without
۰ be given a copy of the signed and dated consent form;
۰ and be given the opportunity to decide to consent or not to consent to a medical
experiment without the intervention of any element of force, fraud, deceit,
duress, coercion or undue influence on the subject's decision.
NOTE: The following paragraph and signature lines should appear on a page with another part of
the consent, it should not start a page.
YOUR SIGNATURE INDICATES THAT YOU HAVE READ AND UNDERSTAND THE ABOVE
INFORMATION, THAT YOU HAVE DISCUSSED THIS STUDY WITH THE PERSON
OBTAINING CONSENT, THAT YOU HAVE DECIDED TO PARTICIPATE BASED ON THE
INFORMATION PROVIDED, AND THAT A COPY OF THIS FORM HAS BEEN GIVEN TO YOU.
Signature of Participant Date
Person Obtaining Consent
I attest that the requirements for informed consent for the medical research project described in
this form have been satisfied – that the participant has been provided with the Experimental
Subject’s Bill of Rights, if appropriate, that I have discussed the research project with the
participant and explained to him or her in nontechnical terms all of the information contained in
this informed consent form, including any risks and adverse reactions that may reasonably be
expected to occur. I further certify that I encouraged the participant to ask questions and that all
questions asked were answered.
Signature of Person Obtaining Consent Date
(If consent is to be obtained from a parent(s), legal guardian or conservator, signature line(s) for
Parent or Guardian must be included on the consent form.)
Signature of Parent or Guardian Date
*Approval Date: ____________________ Expiration Date: __________________
RECOMMENDED TERMS FOR USE IN CONSENT FORMS
To facilitate understanding of consent forms by the subject, it is recommended that the
language used is at a reading level of an 12 year old. The following lay terms, definitions and
suggestions are recommended to help investigators in this process.
Term Lay Definition
abdominal the body cavity containing the stomach, intestines, liver, and other
acute new; recent; sudden
adjuvant helpful; assisting; aiding
adverse effect bad side effect
allergic reaction itching and swelling; rash; trouble breathing
ambulate (-ation –ory) walk; able to walk; ability to walk
ameliorate make smaller or less, reduce
analgesia pain relief
anaphylactic reaction a severe and sometimes dangerous reaction which may cause
problems breathing, fainting, itching and skin rash
anemia low red blood cell count
anesthetic (local) a drug used to decrease the feeling of pain by numbing an area of
the body, without putting you to sleep.
anesthetic (general) a drug used to decrease the feeling of pain or eliminate the feeling of
pain by putting you to sleep.
anorexia lack of appetite
arrhythmia abnormal heartbeat
aspiration removal by using a sucking machine; fluid entering the lungs
asymptomatic without symptoms; having no symptoms
barrier method diaphragm and condom (with spermicide), cervical
cap, or sponge
benign not malignant; usually without serious consequences
bolus an amount given all at once
bradycardia slow heartbeat
carcinogenic capable of causing cancer
carcinoma a type of cancer
catheter a tube in a vein for withdrawing or putting fluids into my blood
central nervous system the brain and spinal cord
cerebral the brain; of the brain
CHD coronary heart disease; heart disease
chemotherapy treatment of a disease, usually cancer, with chemical agents
chronic continuing for a long time
clinical status state of health, how you are doing and feeling
clinical trial an experiment in patients
congenital occurring prior to birth, due to parent’s genetic input
conjunctivitis irritation and redness of the thin covering of the eye
consequences result or effects
controlled trial study in which the experimental treatment is compared to a standard
conventional therapy standard treatment
coronary pertaining to the blood vessels that supply the heart
CT (CAT) scan computerized series of x-rays
cutaneous relating to the skin
culture take a sample of blood, fluid, or tissue to see if bacteria or
viruses can be found in it
dehydration loss of fluids
dermatologic pertaining to the skin
diastolic the lower number in a blood pressure reading
dilation expansion or stretching
discomfort pain; uncomfortable feeling
disseminated widely-spread, all through the body
distal toward the end; away from the center of the body
diuretic water pill; drug that causes an increase in urination
double-blind neither the subject nor physician can know what is being
dysfunction improper function
dysplasia abnormal cells
echocardiogram sound wave test of the heart
edema fluid in the tissues; puffiness; swelling
efficacy producing a positive result
electrocardiogram heart test; tracing of heartbeat or heart rhythm
endoscopic examination of the inside of the body with a lighted tube
epidural outside the spinal cord
eradicate get rid of
erythrocyte red blood cell
FDA Food and Drug Administration; the branch of the government that
approves new drugs
fibrillation irregular heartbeat
fibrous like scar tissue
gastrointestinal stomach and intestines
granulocyte white blood cell
hematocrit number of red blood cells
hematoma bruise; black and blue mark
holter monitor portable machine for recording heartbeats
hormonal therapy treatment with hormones
hypertension high blood pressure
hypotension low blood pressure
hypoxia low oxygen level in the blood
immunosuppressive a drug or therapy that reduces the body’s ability to fight infection;
helps prevent rejection of a transplanted organ
incidence number of times it happens
infarct death of tissue due to loss of blood flow
infectious occurrences infections
inflammation swelling which is usually painful, red and warm
infusion putting a substance into the body, usually into the blood
intravenous putting it into the vein
intubate the placement of a tube into the airway
ischemia decrease in oxygen in a tissue, usually because of decreased blood
lactating producing milk
laparotomy a procedure where an incision is made in the abdominal wall to
enable a physician to look at the organs
lethargy sleepiness; lack of energy
lumen cavity of an organ; inside a blood vessel
lymphocyte a type of white blood cell important for defense against infections
malaise feeling bad; a feeling of bodily discomfort
malignancy cancer which usually spreads and may be fatal if not successfully
marrow suppression decreased growth of the bone marrow
metastasis spread of cancer cells from one part of the body to another
monoclonal antibody very specific, purified antibody
motility the ability to move
MRI pictures of the body created using magnetic rather than x-ray energy
murine obtained from mice
myalgia muscle aches
myocardial infarction heart attack
nasogastric tube a tube from the nose to the stomach
necrosis death of tissue
neoplasia a tumor that may be cancerous or non-cancerous
neural brain or nerves
neutropenia decrease in white blood cells
non-invasive not breaking, cutting or entering the skin
obviate to prevent
occlusion closing; obstruction
occult blood test testing a stool sample for trace amounts of blood
oncology the study of tumors or cancer
ophthalmic pertaining to the eye
orthopedic pertaining to bones
osteoporosis bone disorder resulting from loss of bone leading to increased risk of
ovaries female sex glands that release the egg cells
pancytopenia low number of blood cells
percutaneous through the skin
PROTOCOL REVIEW STANDARDS
CHECK QUESTIONS FOR HEC DISCUSSION
1) The proposed research design is scientifically sound & will not unnecessarily expose
subjects to risk.
a) Is the hypothesis clear? Is it clearly stated?
b) Is the study design appropriate to prove the hypothesis?
c) Will the research contribute to generalizable knowledge and is it worth exposing subjects
2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and
the importance of knowledge that may reasonably be expected to result.
a) What does the EC consider the level of risk to be?
b) What does the PI consider the level of risk/discomfort/ inconvenience to be?
c) Is there prospect of direct benefit to subjects?
3) Subject selection is equitable.
a) Who is to be enrolled? Men? Women? Ethnic minorities? Children (rationale for
inclusion/exclusion addressed)? Seriously-ill persons? Healthy volunteers?
b) Are these subjects appropriate for the protocol?
4) Additional safeguards required for subjects likely to be vulnerable to coercion or undue
a) Are appropriate protections in place for vulnerable subjects, e.g., pregnant women,
fetuses, socially- or economically-disadvantaged, decisionally-impaired?
5) Informed consent is obtained from research subjects or their legally authorized
a) Does the informed consent document include the eight required elements?
b) Is the consent document understandable to subjects? ‘
c) Who will obtain informed consent (PI, nurse, other?) & in what setting?
d) If appropriate, is there a children’s assent?
e) Is the EC requested to waive or alter any informed consent requirement?
6) Subject safety is maximized.
a) Does the research design minimize risks to subjects?
b) Would use of a data & safety monitoring board or other research oversight process
enhance subject safety?
7) Subject privacy & confidentiality are maximized.
a) Will personally-identifiable research data be protected to the extent possible from access
b) Are any special privacy & confidentiality issues properly addressed, e.g., use of genetic
8) Additional considerations
1. Ionizing radiation. If ionizing radiation is used in this protocol is it medically indicated or
for research use only?
2. Collaborative research. Is this domestic/international collaborative research? If so, are
SPAs or other assurances required for the sites involved?
Definition : Minimal risk means that the probability and magnitude of harm or discomfort
anticipated in the research are not greater in and of themselves than those ordinarily
encountered in daily life or during the performance of routine physical or psychological
examinations or tests
Check appropriate risk category:
1. The research involves no more than minimal risk to subjects.
2. The research involves more than minimal risk to subjects.
-The risk(s) represents a minor increase over minimal risk, or
-The risk(s) represents more than a minor increase over minimal risk
Definition: A research benefit is considered to be something of health-related, psychosocial, or
other value to an individual research subject, or something that will contribute to the acquisition
of generalizable knowledge. Money or other compensation for participation in research is not
considered to be a benefit, but rather compensation for research-related inconveniences.
Check appropriate benefit category:
1. The research involves no prospect of direct benefit to individual subjects, but is likely to
yield generalizable knowledge about the subject’s disorder or condition.
2. The research involves the prospect of direct benefit to individual subjects.