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INTRODUCTION
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.
- One should identify the realistic courses of action available
- One should consider whom each course of action would
most benefit and what possible harm could derive from
each
- 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 consideration.
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.
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
research.
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.
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."
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 research.
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 benefits.
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.
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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.
PURPOSE
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 interests.
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 activities.
Mandate
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.
HEC has responsibility within the institution for the following
objectives:
- 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
- Patient care services
- Clinical ethics consultation
- Education of professional, administrative, and support
staff about ethical issues
- Continuing education and training programs that assure
that HEC members are qualified to perform their specific
duties within the HEC.
COMPOSITION
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 bias.
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,
- integrity, and
- diplomacy.
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.
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.
The composition may be as follows:-
- Chairperson
- 1-2 basic medical scientists.
- 1-2 clinicians from each specialty
- One legal expert or retired judge
- One social scientist / representative of non-governmental
voluntary agency
- One philosopher / ethicist / theologian
- One lay person from the community
- Member Secretary
MEMBERSHIP
- All members are nominated by the Director TMC in consultation
with the Chairperson and Member, Secretary.
- Conflict of 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.
TERMS OF APPOINTMENT
Duration
The members of the Tata Memorial Hospital Ethics Committee
will be appointed for duration of 2 years.
Renewal
The membership may be renewed after the stated term of 2 years.
Replacement procedure
The members may be replaced at the discretion of the appointing
authority for the same.
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 grounds
Voting status
All nominated members have the right to vote.
CONDITIONS OF APPOINTMENT
Name, age, gender, profession, and affiliation will be publicized
whenever the committee is reconstituted or there is a change
in the membership.
Conflict of interest to be disclosed if any exists.
Members must apprise themselves of the relevant documents,
codes, GCP, ICH guidelines and the ICMR code.
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.
OFFICERS
The Ethics Committee will have the following
Office bearers who have the expertise and professional qualification
to review what comes in.
Chairperson
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 nonprofessional sources.
Secretary
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.
QUORUM REQUIREMENTS
More than half the minimum number of members is required
to be present to compose a quorum.
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.
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.
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.
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Application
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.
DOCUMENTATION
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 participants;
- 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 applicable;
- 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.
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:
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 emergency procedures;
- the manner in which the results of the research will be
reported and published;
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 research;
- the adequacy of medical supervision and psycho-social
support for the research participants;
- steps to be taken if research participants voluntarily
withdraw during the course of the research;
- 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;
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.
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 representative(s);
- 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.
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 needs;
- 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.
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.
MEETING REQUIREMENTS
HEC will meet at 8.30 am on the last Friday of every month
unless otherwise specified.
The meeting requirements are:
- HEC members will be given all the relevant documents
at least one week in advance of the meeting for review;
- Meetings will be minuted and the minutes approved in
the subsequent meeting;
- The applicant, sponsor, and/or investigator may be invited
to present the proposal or elaborate on specific issues;
- Independent consultants may be invited to the meeting
or to provide written comments, subject to applicable confidentiality
agreements.
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 subjects.
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.
DECISION-MAKING
In making decisions on applications for the ethical review
of biomedical research, the HEC will take the following into
consideration:
- 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;
- 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.
- Decisions will only be made at meetings where a quorum
is present.
- The documents required for a full review of the application
should be complete and the relevant elements considered
before a decision is made.
- Only members who participate in the review will participate
in the decision.
- Decisions will be arrived at through consensus, where
possible; when a consensus is not possible, the HEC will
vote.
- Any advice that is non-binding will be appended to the
decision.
- In cases of conditional decisions, clear suggestions
for revision and the procedure for having the application
re-reviewed will be specified.
- A negative decision on an application will be supported
by clearly stated reasons.
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.
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.
FOLLOW-UP
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.
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 Monitoring Subcommittee.
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.
In the case of the premature suspension/termination of a study,
the applicant must notify the HEC of the reasons for suspension/termination.
A summary of results obtained in a study prematurely suspended/terminated
should be communicated to the HEC.
HEC should receive notification from the applicant at the
time of the completion of a study
HEC should receive a copy of the final summary or final report
of a study.
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.
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) reports;
- 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 study;
- the final summary or final report of the study.
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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.
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.
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.
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Tata Memorial Hospital, Dr.
E Borges Road, Parel, Mumbai - 400 012 India. 