Chapter 20 · Evidence, ethics and publishing

What protects the people you study?

ICMR guidelines, informed consent, ethics committees, vulnerable groups and animal research.

31 TNMGRMU questions answered hereset 35 times, 2001–2025

The problem first

You are an MD Medicine resident. Your thesis asks why patients at the ART centre miss their HIV medicines. It is only a questionnaire, so you start interviewing patients in the waiting area and plan to send the protocol to the ethics committee later.

A relative sitting nearby hears one interview and learns the patient's HIV status. At the viva the examiner asks one question.

“Who decided that your study did not need ethics review?”

Start here

Why does research need its own ethical rules?

Treatment is given for the benefit of the patient in front of you. Research is done to produce knowledge for future patients, and the participant carries the risk. The rules make sure that risk is justified, explained to the participant, and checked by people independent of the researcher.

ICMR 2017 (section 1.0) states that every research study carries some risk of harm or inconvenience, so protection of participants should be built into the design. The 2024 Declaration of Helsinki (para 7) says the purposes of research can never take precedence over the rights and interests of individual participants.

1Write the protocolethical sections included, scientific review first2Ethics committeeapproval before any participant is enrolled3Register the studyCTRI, before the first participant is recruited4Take consentfrom each participant, before any study procedure5Report while it runsSAE to the EC in 24 h, progress and final reportsthe EC decides the type of review, not the researcher
Five checkpoints, in this order. The ethics committee (EC) approves before enrolment. A trial is registered before the first participant is recruited. Consent comes before any study procedure. Serious adverse events (SAEs) go to the EC within 24 hours (ICMR 2017, 2.6.1).

ICMR 2017

Which principles does ICMR ask you to follow?

ICMR starts from four basic principles: respect for persons (autonomy), beneficence, non-maleficence and justice. It expands them into 12 general principles that apply to all biomedical, social and behavioural research for health.

ICMR 2017 principleWhat it requires
1. EssentialityUsing human participants is essential after considering all alternatives, vetted by an independent EC
2. VoluntarinessThe right to agree, refuse or withdraw at any time
3. Non-exploitationFair selection of participants, with safeguards for vulnerable groups
4. Social responsibilityResearch must not create or deepen social divisions
5. Privacy and confidentialityIdentity and records kept confidential, breached only in defined situations, in consultation with the EC
6. Risk minimisationRisks minimised at every stage, with care and compensation if harm occurs
7. Professional competenceResearch run by people with the right qualification, experience or training
8. Maximisation of benefitDesign that increases benefit to participants or society
9. Institutional arrangementsInstitutions provide governance, infrastructure, staff, funds and training
10. Transparency and accountabilityRegistration, publication of outcomes, declared conflicts of interest, records kept
11. Totality of responsibilityEvery stakeholder is responsible for their actions
12. Environmental protectionResearchers protect the environment and resources

The 2006 ICMR guidelines also had 12 principles, with slightly different names (for example, “precaution and risk minimisation”, “public domain” and “compliance”). Examiners who ask for “ICMR principles” now expect the 2017 list.

Types of review

Does every study need full ethics committee review?

Every proposal must be submitted. The Member Secretary screens it and the EC decides whether it is exempt, expedited or needs full committee review, based on risk.

Less than minimal riskanonymised data, meta-analysisMinimal riskhistory, examination, urine sampleMinor increase over minimalsmall blood sample, childrenMore than minimal riskdrug, device, biopsy, endoscopyExemption from reviewno linked identifiersExpedited reviewChair, Member Secretary, 1–2 membersFull committee reviewalso any study on a vulnerablegroup, even at minimal risk
Risk categories from ICMR 2017 Table 2.1, review types from Table 4.2. Research on vulnerable populations goes to full committee review even when the risk is minimal. Exempt and expedited decisions are ratified at the next full committee meeting (4.8.5).

“A researcher cannot decide that her/his proposal falls in the exempted, expedited or full review category” (ICMR 2017, 4.8.3). A retrospective record review still goes to the EC. The EC may then exempt it, or grant a waiver of consent.

Interactive

Choose the type of review for each proposal, then read the reason

Six made-up proposals, sorted with ICMR 2017 Tables 2.1 and 4.2 and Box 6.2.

Try this: choose a type of review for each made-up proposal, then read the reason. Compare proposals 2 and 3, which use the same questionnaire.

In practice the Member Secretary screens the proposal and the EC decides the category. The researcher only submits it.

  1. A meta-analysis of published trials, using only data available in the public domain.

  2. A questionnaire and a blood pressure measurement in adult outpatients at a medicine clinic.

  3. The same questionnaire, given to people living with HIV at the ART centre.

  4. One small blood sample from each healthy adult volunteer, to measure a vitamin level.

  5. A randomised trial comparing a new drug with the standard drug.

  6. A questionnaire about study habits, given to the MBBS students you teach.

Vulnerable groups

Who counts as vulnerable, and what changes?

Vulnerable people are relatively or absolutely unable to protect their own interests. The cause may be legal (children), clinical (cognitive impairment, unconsciousness) or situational (poverty, hierarchy, institutional life).

ICMR 2017 (Box 6.2) lists, among others, economically and socially disadvantaged people, children up to 18 years, pregnant or lactating women, tribal and marginalised communities, refugees and migrants, people with mental illness or cognitive impairment, the terminally ill, people with stigmatising or rare diseases, and people in a hierarchy (students, employees, healthcare workers, defence personnel and prisoners).

  • They have an equal right to be included, so that the benefits of research apply to them (6.1.1).
  • If a vulnerable group is recruited alone, the research must answer that group's health needs (6.1.2).
  • The researcher justifies their inclusion. The EC records its decision and reviews the protocol at full committee only (6.2, Table 6.1).
  • The 2024 Declaration of Helsinki (para 19) asks that the harms of exclusion be weighed against the harms of inclusion.

People living with HIV

HIV status is sensitive information that can lead to stigma (2.3.4). Confidentiality can be breached for HIV positive status only in consultation with the EC, for valid scientific or legal reasons (1.1.5). In HIV trials, testing needs consent with pre-test and post-test counselling as per NACO guidelines, and the right to life of the sexual partner is respected over the right to privacy (7.12). In trials of anti-HIV drugs, the NDCT Rules require an audio recording (not video) of the consent process.

People with mental illness

ICMR uses the Mental Healthcare Act, 2017 definition of mental illness and states that a mental disorder is not the same as inability to give consent. If the person cannot consent, the LAR consents, and the person's own consent is taken once competence returns. The consent process must explain how suicidal ideation will be handled and that confidentiality may be breached to protect the participant (6.8).

FeatureConsentAssent
Given byA competent adult, or the LAR on behalf of someone who cannot consentA child (or an adult who cannot consent) who can still understand and agree
Legal weightLegally valid permissionAgreement that must be respected, given in addition to LAR consent
Age bands (ICMR 2017)18 years and aboveUnder 7: not documented; 7–12: verbal, recorded; 12–18: written
If the person objectsNo enrolmentThe objection is respected. Failure to object is not assent
ExceptionWaiver by the EC in defined situationsChild’s dissent may be overridden only if the intervention may be lifesaving, with parental consent and EC approval

Ethics committee

Who sits on an ethics committee, and what does it do?

ICMR 2017 recommends 7 to 15 members, preferably half from outside the institution, with a quorum of at least 5. The head of the institution appoints the members but should not sit on the committee.

ChairpersonoutsideMemberSecretaryinsideBasic medicalscientisteitherClinicianeitherLegal experteitherSocial scientistor ethicisteitherLay personoutsideTrial ECs (NDCT rule 7): at least 7 members, at least half from outside,at least one woman, one lay person and one legal expert
Red: must be from outside the institution. Black: must be from inside. Grey: either. The lay person is literate, has not had a medical or health career in the last 5 years, and reviews the consent document and the benefits and risks from the participant's point of view (ICMR 2017, Table 4.1).

What the committee does (ICMR 2017, 4.7)

  • Protects the dignity, rights, safety and well-being of participants.
  • Reviews scientific, ethical, medical and social aspects before the study (initial review) and during it (continuing review).
  • Reviews progress reports, final reports, adverse events and SAEs, and recommends compensation for research-related injury.
  • Carries out monitoring visits at study sites when needed.
  • Records conflicts of interest of members at each meeting.

Quorum (Box 4.2): at least 5 members present, both medical and non-medical or technical and non-technical, at least one non-affiliated member, preferably including the lay person. No decision is valid without a quorum.

NDCT Rules 2019

How does an ethics committee get registered?

An EC that approves clinical trials registers with the Central Licencing Authority (CDSCO). An EC for other biomedical and health research registers with the authority designated by the Department of Health Research.

  1. The institution constitutes the EC as required by rule 7 (for trials) or the ICMR guidelines (rule 16, for other research).
  2. The EC applies in Form CT-01 with the documents in Table 1 of the Third Schedule (rules 8 and 17).
  3. The Central Licencing Authority scrutinises the application and grants registration in Form CT-02, or rejects it with written reasons, within 45 working days.
  4. If there is no reply in 45 working days, registration is deemed granted. The EC informs the authority in Form CT-02A before starting work.
  5. Registration is valid for 5 years (rule 9). Apply for renewal 90 days before expiry (rule 10).
  6. A rejected EC can appeal to the Central Government within 60 working days.

Compensation

Who pays when a participant is harmed?

Two different payments are often confused. Reimbursement pays participants for their time and expenses. Compensation pays for injury or death caused by the research.

FeaturePayment for participationCompensation for research-related harm
PurposeTravel, lost wages, time, food and incidental expensesInjury, permanent disability or death related to the research
Given toAll participants, as approvedThe injured participant, or the legal heir after a death
Decided byEC approves the amount so it is not an undue inducementEC, and for regulated trials the Central Licencing Authority using the NDCT formula
Paid byThe research budgetThe sponsor, or the institution in student or investigator-initiated research
SourceICMR 2017, 2.5ICMR 2017, 2.6; NDCT Rules 2019, rules 39–42 and Seventh Schedule

In a clinical trial, the sponsor gives free medical management for any injury for as long as the investigator thinks it is needed, or until the injury is shown to be unrelated (rule 40). Financial compensation is in addition to this (rule 39). Rule 41 treats an injury as trial-related if it is caused by the investigational product, a protocol violation or negligence, failure to give standard care or rescue medication that was available, a concomitant medicine required by the protocol, an effect on a child in utero, or any trial procedure.

Investigator reports SAE24 hSponsor and investigator reports14 dEC opinion on compensation30 dExpert committee recommends60 dLicensing authority decides90 dSponsor pays120 d0306090120days after the SAE
After a death in a clinical trial (rule 42(2)). Each deadline is a maximum. The EC’s 30 days run from receiving the investigator’s report. The sponsor pays within 30 days of the authority’s order, which can be up to about day 120.

Compensation for death = (B × F × R) ÷ 99.37

B
base amount, ₹8 lakh
F
age factor from Annexure 1 of the Seventh Schedule (228.54 at 16 years, falling to 99.37 at 65 years or more)
R
risk factor at enrolment: 0.5 terminally ill, 1.0 high risk, 2.0 moderate, 3.0 mild, 4.0 healthy volunteer

If expected mortality is 90% or more within 30 days, a fixed ₹2 lakh is paid instead.

Teaching example 1. A 30-year-old healthy volunteer dies from a trial-related SAE. F = 207.98, R = 4.0.

8,00,000 × 207.98 × 4.0 ÷ 99.37 = ₹66,97,555

Teaching example 2. A 45-year-old patient at moderate risk (F = 169.44, R = 2.0) is left with 50% permanent disability.

C = 8,00,000 × 169.44 × 2.0 ÷ 99.37 = ₹27,28,228 → C × 50 × 90 ÷ (100 × 100) = ₹12,27,703

For permanent disability, 100% disability earns 90% of the death amount (C), in proportion to the percentage of disability. For a reversible SAE or chronic life-threatening disease, compensation = 2 × W × N, where W is the daily minimum wage of an unskilled worker in Delhi and N is the number of days in hospital.

Interactive

Change the age, risk factor and outcome, and watch the compensation change

The death and permanent disability formulas of the NDCT Rules 2019, Seventh Schedule, with the age factors of Annexure 1.

Try this: keep the age at 30 and change the risk factor from 4.0 (healthy volunteer) to 0.5 (terminally ill). Watch how much the amount falls.

Made-up participant. Formula from the NDCT Rules 2019, Seventh Schedule. Free medical management for the injury (rule 40) is in addition to this amount.

Outcome
30

Age factor F = 207.98 (Annexure 1)

Risk factor R at enrolment

R = 4.0: healthy volunteer or participant with no risk

Expected mortality

For such patients the schedule gives a fixed ₹2 lakh instead of the formula

₹66,97,555compensation for death

8,00,000 × 207.98 × 4.0 ÷ 99.37 = ₹66,97,555

A participant aged 30 with risk factor 4.0 receives ₹66,97,555. The amount is larger for a younger participant (larger F) and for a healthier participant at enrolment (larger R).

International codes

Where did these rules come from?

Each major code followed a failure. Doctors experimented on prisoners in Nazi Germany, and the Nuremberg Code followed. In the United States, men with syphilis were left untreated from 1932 to 1972, and the Belmont Report followed.

Nuremberg Code (1947). Ten points in the August 1947 verdict of the doctors' trial (USA v. Karl Brandt et al.). Point 1: “The voluntary consent of the human subject is absolutely essential.”

Belmont Report (1979). Written by the US National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and published on 18 April 1979. Three principles: respect for persons, beneficence and justice. Three applications: informed consent, assessment of risks and benefits, and selection of subjects.

Declaration of Helsinki. Adopted by the World Medical Association (WMA) in Helsinki in June 1964. The current version is the 2024 revision, adopted in Helsinki in October 2024 and published in JAMA in January 2025. Its title now says “human participants” where the 2013 version said “human subjects”.

FeatureNuremberg Code (1947)Declaration of Helsinki (2024)
Issued byA US military tribunal, as part of a verdictThe World Medical Association
Length10 points37 paragraphs
People who cannot consentNot addressed. The subject must have legal capacityConsent from the legally authorised representative, plus assent where possible (paras 28–30)
Ethics committeeNot mentionedMust approve the protocol before research begins, and includes at least one member of the public (para 23)
PlaceboNot mentionedOnly if no proven intervention exists, or for compelling methodological reasons without risk of serious or irreversible harm (para 33)
Registration and publicationNot mentionedRegister before the first participant, and publish negative and inconclusive results (paras 35–36)
RevisionsNoneAmended 1975, 1983, 1989, 1996, 2000, 2008, 2013 and 2024

Good clinical practice

What is good clinical practice?

Good clinical practice (GCP) is the international standard for designing, conducting, recording and reporting clinical trials. The ICH guideline is E6. The current version, E6(R3), was adopted on 6 January 2025, replacing E6(R2) of 9 November 2016.

  1. Follow the ethical principles that originate in the Declaration of Helsinki. Participants' rights, safety and well-being come before the interests of science and society.
  2. Informed consent, freely given and documented.
  3. Independent review by an IRB/IEC.
  4. Scientifically sound, based on adequate current knowledge.
  5. Designed and conducted by qualified individuals.
  6. Quality built into design and conduct (quality by design).
  7. Processes proportionate to the risks to participants and the importance of the data.
  8. A clear, concise, scientifically sound and operationally feasible protocol.
  9. Reliable results, with timely registration and public posting of results.
  10. Clear, documented roles and responsibilities.
  11. Investigational products manufactured to Good Manufacturing Practice.

In the European Union, the E6(R3) principles and Annex 1 took effect on 23 July 2025. Annex 2 (pragmatic and decentralised trials, real-world data) takes effect on 15 January 2027. In India, NDCT rule 7(6) requires EC members to follow GCP guidelines, and CDSCO issued Indian GCP guidelines in 2001. Trial design is covered in the clinical trials chapter.

Animal research

What rules apply to animal experiments?

In India, animal experiments come under the Prevention of Cruelty to Animals Act, 1960, and the Breeding of and Experiments on Animals (Control and Supervision) Rules, 1998. The national committee is CCSEA, which was called CPCSEA until January 2023.

ReplacementReductionRefinementcells, tissue or acomputer model insteadthe minimum number thatgives a valid resultanaesthesialess pain and distress,stop if pain is severe
The 3Rs, from William Russell and Rex Burch, The Principles of Humane Experimental Technique (1959). Indian rules state them directly: use animals lowest on the phylogenetic scale that give valid results, the minimum number for a statistically valid result, and justify not using a replacement alternative when one exists (rule 9(bb), amended 2006).
From the institution (5)1 biological scientist2 scientists, different biological disciplines1 veterinarian (mandatory)1 scientist in charge of the animal houseNominated by CCSEA (3)main nomineescientist from outside the institutesocially aware nomineedashed: link nominee, replaces themain nominee when absentquorum 6, and the main nominee must be present
The Institutional Animal Ethics Committee (IAEC) under the CCSEA standard operating procedure. The Chairperson and Member Secretary are chosen from the five institutional members. The IAEC approves experiments on small animals such as rodents. For larger animals it forwards its recommendation to CCSEA.
FeatureInstitutional Ethics Committee (human)Institutional Animal Ethics Committee
ProtectsHuman participants, their samples and dataAnimals, before, during and after experiments
Legal basisNDCT Rules 2019; ICMR 2017 guidelinesPCA Act 1960; Breeding and Experiments Rules 1998
Registered withCDSCO (trials) or DHR-designated authorityCCSEA
MembersAt least 7 for trial ECs8: five internal and three CCSEA nominees
Outside membersAt least half, with the Chairperson from outsideCCSEA nominees, including a socially aware member
QuorumAt least 5 (ICMR)At least 6, with the main nominee present

Publication ethics

Where does publication ethics fit?

Ethics continues after the data are collected. ICMR 2017 requires completed research to be published whatever the result, and authorship to follow the four ICMJE criteria.

Plagiarism, duplicate publication, predatory journals and authorship disputes are covered in the publishing and IPR chapter.

By specialty

Research ethics problems by specialty

A thesis on why patients with HIV miss doses of antiretroviral therapy, using interviews at the ART centre.

HIV status is sensitive information (ICMR 2017, 2.3.4). Interview in private, keep names off the forms, and explain the limits of confidentiality before consent.

Common myths

Common mistaken beliefs

  • Myth: A thesis that uses only a questionnaire does not need ethics committee approval.

    All types of biomedical and health research must be reviewed by an EC (ICMR 2017, 4.0.4). The EC, not the researcher, decides whether a study is exempt (4.8.3).

  • Myth: A signed consent form means consent was informed.

    Consent is a continuous process of information, understanding and a voluntary decision (ICMR 2017, 5.0). Re-consent is needed when new information changes the risks or benefits.

  • Myth: Paying participants is always undue inducement.

    Reimbursement for travel, lost wages and time is allowed when the EC approves it (ICMR 2017, 2.5). It is separate from compensation for injury.

  • Myth: Vulnerable groups should be kept out of research.

    They have an equal right to be included so that the benefits apply to them (ICMR 2017, 6.1.1). The 2024 Declaration of Helsinki asks that the harms of exclusion be weighed against the harms of inclusion.

  • Myth: The latest Declaration of Helsinki is the 2013 Fortaleza version.

    The current version was adopted in October 2024 at the WMA General Assembly in Helsinki.

  • Myth: ICH E6(R2) is the current GCP guideline.

    ICH E6(R3) was adopted on 6 January 2025.

Why this matters to you

Five consequences of ignoring research ethics

  1. Protocol returned by the EC

    ICMR 2017 (Box 4.4) expects the protocol to describe the consent procedure, confidentiality, and compensation for research-related injury. A protocol without them is sent back.

  2. A trial that journals question

    Clinical trials must be registered with CTRI (ICMR 2017, 7.1.10), before the first participant is recruited (Declaration of Helsinki 2024, para 35).

  3. A paper that should not be accepted

    The Declaration of Helsinki (para 36) says reports of research that did not follow its principles should not be accepted for publication.

  4. Questions you cannot answer at the viva

    Which version of the Declaration of Helsinki, and which ICMR guideline, did you follow? The answers are the 2024 revision and the 2017 national guidelines.

  5. A harmed patient and no plan

    In student and investigator-initiated research the institution is the sponsor and must provide for compensation (ICMR 2017, 2.6.4). SAEs must reach the EC within 24 hours.

History

History of research ethics

  1. 1947

    Nuremberg Code

    Ten points set out in the August 1947 verdict of the doctors’ trial. The first: voluntary consent of the human subject is absolutely essential.

  2. 1959

    William Russell and Rex Burch

    Published The Principles of Humane Experimental Technique, which introduced replacement, reduction and refinement (the 3Rs).

  3. 1960

    Parliament of India

    Prevention of Cruelty to Animals Act, under which the committee now called CCSEA is constituted.

  4. 1964

    World Medical Association

    Adopted the Declaration of Helsinki at its 18th General Assembly in Helsinki, June 1964.

  5. 1972

    Tuskegee study ends

    A US Public Health Service study (1932–1972) followed Black men with syphilis without telling them the diagnosis or treating them, and ended after it was made public in July 1972.

  6. 1979

    Belmont Report

    Published on 18 April 1979. Set out respect for persons, beneficence and justice.

  7. 1980

    ICMR

    Policy Statement on Ethical Considerations Involved in Research on Human Subjects, under Justice H R Khanna. Revised in 2000 and 2006.

  8. 1996

    ICH E6

    Good clinical practice guideline reached Step 4 on 1 May 1996. E6(R2) followed on 9 November 2016.

  9. 2009

    CDSCO and CTRI

    Registration in the Clinical Trials Registry–India, launched by ICMR in 2007, became mandatory for regulated trials on 15 June 2009.

  10. 2017

    ICMR

    National Ethical Guidelines for Biomedical and Health Research Involving Human Participants, October 2017, in 12 sections.

  11. 2019

    Government of India

    New Drugs and Clinical Trials Rules notified on 19 March 2019 (G.S.R. 227(E)).

  12. 2023

    CPCSEA renamed CCSEA

    A letter dated 6 January 2023 changed the name to Committee for Control and Supervision of Experiments on Animals.

  13. 2024

    World Medical Association

    Adopted the revised Declaration of Helsinki at its General Assembly in Helsinki, October 2024.

  14. 2025

    ICH E6(R3)

    Adopted on 6 January 2025.

Guidelines

Research ethics in guidelines and law

ICMR 2017, section 4.8.3

“A researcher cannot decide that her/his proposal falls in the exempted, expedited or full review category. All research proposals must be submitted to the EC.”

NDCT Rules 2019, rule 7

An EC for clinical trials has “a minimum of seven members from medical, non-medical, scientific and non-scientific areas”, with at least one lay person, one woman, one legal expert and one independent member such as a social scientist, ethicist or theologian. At least 50% are not affiliated with the institution. The Chairperson is from outside and the Member Secretary from inside.

NDCT Rules 2019, rule 42(1)

The investigator reports all serious adverse events to the Central Licencing Authority, the sponsor and the EC “within twenty-four hours of their occurrence”.

Declaration of Helsinki 2024, para 35

“Medical research involving human participants must be registered in a publicly accessible database before recruitment of the first participant.”

ICH E6(R3), principle 1.1

“The rights, safety and well-being of the participants are the most important considerations and should prevail over interests of science and society.”

Breeding of and Experiments on Animals Rules 1998, rule 9(bb), amended 2006

Animals lowest on the phylogenetic scale that give scientifically valid results are considered first. The minimum number of animals is used. Replacement alternatives are given full consideration.

Steps

Getting ethics approval for your thesis, step by step

  1. Write the protocol with its ethical sections: justification for including vulnerable groups, consent procedure, confidentiality, compensation plan and publication plan (ICMR 2017, Box 4.4).
  2. Get scientific review first, if your institution has a scientific committee (4.3.12).
  3. Prepare the information sheet and consent form in English and the local language, with translation certificates.
  4. Submit to the Member Secretary: cover letter, application form, CVs, conflict of interest statement, and GCP training certificates for trials.
  5. Wait for approval. Do not enrol anyone before it.
  6. Register a clinical trial with CTRI before the first participant is recruited.
  7. Take consent before any study procedure (5.1.4).
  8. Report SAEs to the EC within 24 hours and send a report on relatedness within 14 days (2.6.1). Submit progress and final reports.

Reading a paper

Five ethics checks on any study

  • Does the paper name the ethics committee that approved the study?
  • Does it say how consent was obtained, or why the committee waived it?
  • For a trial, is the registration number given, and was it registered before recruitment began?
  • If vulnerable groups were included, is their inclusion justified?
  • Are funding sources and conflicts of interest declared?

Why is it called that?

Word surgery

“Compensation”

In everyday speech

Payment for work, or a salary package.

In research

Money paid for injury or death related to the research. Payment for time and travel is reimbursement, and is separate.

“Vulnerable”

In everyday speech

Weak or easily hurt.

In research

Less able to protect one’s own interests in research. A healthy junior employee can be vulnerable because of the hierarchy.

Memory trick

A trial ethics committee has at least 7 members, at least half from outside, a Chairperson from outside and a Member Secretary from inside, with at least one lay person, one woman and one legal expert.

Ethics

Greek ēthikos "pertaining to character", from ēthos "moral character" and "custom"

The study of what is right conduct. Research ethics applies it to how participants are chosen, informed and protected.

Consent

Latin consentire: "feel together", from com "with" + sentire "to feel"

Agreement to take part, given freely by a person who understands what is proposed.

Autonomy

Greek autos "self" + nomos "custom, law"

A person’s right to decide for themselves. Informed consent is how research respects it.

Vulnerable

Latin vulnerare: "to wound", from vulnus "wound"

At greater risk of being wronged or harmed in research, and in need of extra safeguards.

Compensation

Latin compensare: "to weigh one thing against another"

Payment that balances a harm the participant suffered because of the research.

Exam answers

Model answer outlines

Research ethics: need, ethical principles, and ethical considerations in experimental studies on human beings

Ph.D. RM 2014, 2016, 2017, 2021, 2023, 2025

Scientific research is systematic enquiry aimed at generalisable knowledge. Health research is ethically justified by its social value (ICMR 2017, 1.0). See the what is research chapter.

  1. Need: participants carry risk for the benefit of others. Past abuses (Nazi experiments, Tuskegee 1932–1972) led to the Nuremberg Code (1947) and the Belmont Report (1979).
  2. Basic principles: respect for persons (autonomy), beneficence, non-maleficence and justice (ICMR 2017). Belmont lists respect for persons, beneficence and justice.
  3. ICMR 12 general principles: essentiality, voluntariness, non-exploitation, social responsibility, privacy and confidentiality, risk minimisation, professional competence, maximisation of benefit, institutional arrangements, transparency and accountability, totality of responsibility, environmental protection.
  4. Social value and scientific validity: poor science exposes participants to risk without benefit (Table 4.3).
  5. Benefit–risk assessment by researcher, sponsor and EC (2.1).
  6. EC approval before the study, with the type of review set by risk (exempt, expedited, full).
  7. Informed consent: information, competence, comprehension and voluntariness, 10 essential elements, and rules for waiver and re-consent.
  8. Privacy and confidentiality; limits explained to participants.
  9. Distributive justice and safeguards for vulnerable groups.
  10. Payment for participation (reimbursement) and compensation for research-related harm.
  11. Conflict of interest declared and managed (2.8).
  12. Placebo only under Declaration of Helsinki para 33, and post-trial provisions (para 34).
  13. Registration (CTRI) and publication of all results, positive or negative (ICMR 3.4.3).

ICMR ethical guidelines for human research, including the principles of informed consent and competence

Ph.D. RM 2013, 2015, 2016 · MD Forensic Medicine 2023
  1. History: Policy Statement 1980 (Justice H R Khanna), revised in 2000 and 2006, then the National Ethical Guidelines for Biomedical and Health Research Involving Human Participants, October 2017.
  2. 12 sections (2017):
    1. General principles
    2. General ethical issues
    3. Responsible conduct of research
    4. Ethical review procedures
    5. Informed consent process
    6. Vulnerability
    7. Clinical trials of drugs and other interventions
    8. Public health research
    9. Social and behavioural sciences research for health
    10. Human genetics testing and research
    11. Biological materials, biobanking and datasets
    12. Research during humanitarian emergencies and disasters
  3. Principles: 4 basic principles expanded into the 12 general principles (table above).
  4. Informed consent: voluntary and written, given only by a person with the capacity to understand and decide, free of coercion and undue inducement, and taken before any study procedure. LAR consent for those who cannot consent, an impartial witness for illiterate participants, and audio-video recording where CDSCO requires it. Waiver only by the EC. Re-consent when circumstances change (section 5).
  5. Competence: of the participant (capacity to understand and decide, 5.1.1) and of the researcher (principle of professional competence: qualification, experience and/or training, 1.1.7). The 2006 guidelines called it the “principle of professional competence” as well.
  6. Ethics committee: composition, quorum, types of review, continuing review, record keeping (3 years, or 5 years for regulatory trials).
  7. Vulnerable groups, payment, compensation, confidentiality, conflict of interest, post-research access (sections 2 and 6).

Declaration of Helsinki, and the modified Declaration of Helsinki

MD Pharmacology 2008, 2015 · MD Forensic Medicine 2016
  1. What: the World Medical Association's statement of ethical principles for medical research involving human participants, including identifiable human material and data.
  2. Adopted: 18th WMA General Assembly, Helsinki, June 1964.
  3. Amended: Tokyo 1975, Venice 1983, Hong Kong 1989, Somerset West 1996, Edinburgh 2000, Seoul 2008, Fortaleza 2013, Helsinki October 2024. Notes of clarification were added in 2002 and 2004.
  4. Current version: 2024 (JAMA 2025;333:71–4). The 2013 version was titled “human subjects”. The 2024 version uses “human participants”.
  5. 2024 content to quote:
    • Principles apply to all individuals, teams and organisations in research (para 2).
    • Fair distribution of benefits, risks and burdens, and community engagement (para 6).
    • Public health emergencies (para 8) and environmental sustainability (para 11).
    • Compensation and treatment for harm (para 15).
    • Vulnerability, weighing the harms of exclusion against inclusion (paras 19–20).
    • Ethics committee approval before research, with at least one member of the general public (para 23).
    • Consent documented on paper or electronically (para 26).
    • Placebo (para 33) and post-trial provisions (para 34).
    • Registration before the first participant (para 35) and publication of negative and inconclusive results (para 36).

Institutional ethics committee (institutional review board): organisation, functions, roles, and the lay person

MD Pharmacology 2013, 2016, 2018, 2019, 2021 · MCh Surgical Oncology 2009 · Ph.D. RM 2016

Definition (ICH E6(R3)): an independent body of medical professionals and non-medical members that protects the rights, safety and well-being of participants by reviewing and approving the protocol, the investigators, the facilities and the consent materials. IRB and IEC are names for the same kind of body. Indian rules call it the Ethics Committee.

Member (ICMR Table 4.1)AffiliationRole
ChairpersonNon-affiliatedConducts meetings, ensures quorum and participation, handles complaints and conflicts of interest
Member SecretaryAffiliatedReceives and screens proposals, decides type of review, agenda and minutes, SOPs, training, audits
Basic medical scientistEitherScientific review (preferably a pharmacologist for drug trials)
ClinicianEitherDesign, sample size, site, medical care and compensation provisions
Legal expertEitherConsent document, agreements, insurance, regulatory compliance
Social scientist / ethicist / theologianEitherSocio-cultural context and community concerns
Lay personNon-affiliatedConsent document and benefits and risks from the participant's point of view
  • Organisation: 7–15 members, preferably 50% non-affiliated. The head of the institution appoints members but does not sit on the EC. Term usually 2–3 years. Written SOPs. Members trained in human research protection and GCP.
  • Quorum: at least 5, medical and non-medical, at least one non-affiliated member, preferably the lay person.
  • Functions: initial review and approval, continuing review (progress reports, deviations, SAEs), site monitoring, recommending compensation, keeping records and educating researchers (ICMR 4.7, NDCT rule 11).
  • Lay person: literate member of the public, no medical or health career in the last 5 years, may represent the participants' community, knows the local language and values. Required on trial ECs (NDCT rule 7). The Declaration of Helsinki (para 23) requires at least one member of the general public.

Constitution and registration of an institutional ethics committee for clinical trials, and roles of the Member Secretary and legal expert

MD Pharmacology 2023
  1. Constitution (NDCT rule 7): at least 7 members from medical, non-medical, scientific and non-scientific areas. At least one lay person, one woman, one legal expert and one independent member (social scientist, NGO representative, philosopher, ethicist or theologian). At least 50% not affiliated. A non-affiliated Chairperson and an affiliated Member Secretary, both appointed by the institution. Medical scientists and clinicians with at least postgraduate qualification. Members trained as specified by the Central Licencing Authority. Conflicts of interest declared and recorded. A patient group representative (for example HIV) where relevant.
  2. Registration (rule 8): Form CT-01 with Third Schedule documents → scrutiny → Form CT-02 or rejection within 45 working days → deemed registration (Form CT-02A) if no reply → appeal within 60 working days.
  3. Validity and renewal: 5 years (rule 9), with renewal applied for 90 days before expiry (rule 10).
  4. Member Secretary: a staff member of the institution. Receives, screens and circulates proposals, and assesses the need for exemption, expedited or full review. Schedules meetings and prepares the agenda and minutes. Maintains documentation and archiving. Ensures that SOPs are followed and updated, members are trained and the quorum is met. Prepares for audits and inspections.
  5. Legal expert: a degree in law, with experience. Reviews the consent document and translations, MoUs, clinical trial agreement, regulatory approvals, insurance documents and compliance with guidelines. Informs members about new regulations.

Good clinical practice, including GCP in a clinical research protocol

MD Community Medicine 2025 · MD Pharmacology 2014
  1. Definition: an international ethical and scientific quality standard for trials that protects participants and makes results reliable.
  2. Versions: ICH E6 (1996), E6(R2) (9 November 2016), E6(R3) adopted 6 January 2025. Indian GCP guidelines (CDSCO, 2001).
  3. The 11 E6(R3) principles: ethics (Declaration of Helsinki), informed consent, IRB/IEC review, scientific soundness, qualified individuals, quality by design, risk-proportionate processes, a clear protocol, reliable results, clear roles, GMP-manufactured investigational products.
  4. GCP in the protocol: clear objectives, and a protocol that is clear, concise and operationally feasible, with its statistical analysis, data management and monitoring plans (principle 8). Factors critical to quality identified in advance (principle 6). Registration and results posting (principle 9.6).
  5. Ethical sections ICMR expects in a protocol: justification for vulnerable groups and placebo, consent procedure, confidentiality, management of research-related injury, compensation and reimbursement, ancillary care, data storage, publication plan (Box 4.4). See the research protocol chapter.

Compensation for participation in clinical trials: principles

Ph.D. RM 2019, 2020
  1. Two meanings: payment for participation (travel, lost wages and time, approved by the EC so that it is not an undue inducement) and compensation for research-related injury or death.
  2. ICMR 2017 (2.6): participants harmed as a result of research are entitled to financial or other assistance, and dependents are entitled after a death. This applies to all arms, including control. Medical management is free if the harm is related. The sponsor budgets for insurance or compensation. In student research the institution is the sponsor and may keep a corpus fund.
  3. NDCT Rules 2019: financial compensation by the sponsor for death (to the legal heir), permanent disability or other injury, in addition to medical management (rule 39). Free medical management (rule 40). Causes considered trial-related (rule 41). Procedure and deadlines (rule 42). An undertaking to pay is submitted with the trial application (rule 39(5)).
  4. Formula (Seventh Schedule): death = B × F × R ÷ 99.37 (B = ₹8 lakh, F = age factor, R = risk factor 0.5–4.0). Permanent disability = C × D × 90 ÷ 10,000. Birth defect = half the base amount. Reversible SAE = 2 × daily minimum wage × days in hospital.
  5. Worked example: healthy volunteer aged 30 → ₹66,97,555.
  6. Failure to pay: the licensing authority can suspend or cancel the trial or bar the sponsor from further trials.

(a) Key components of a research protocol. (b) Ethical issues in research involving people with HIV, the mentally ill and other vulnerable groups

Ph.D. RM 2019

(a) Title, summary, background and rationale, objectives, eligibility, methodology with sample size and design, duration, statistical plan, consent procedure, confidentiality plan, risk management and compensation, data storage and publication plan (ICMR 2017, Box 4.4). Details in the research protocol chapter.

(b)

  1. Definition and examples of vulnerability (ICMR section 6, Box 6.2).
  2. General safeguards: justify inclusion, research that answers the group's needs, full committee review, no coercion or incentives, repeated information, strict confidentiality and support systems (6.1–6.2).
  3. HIV: HIV status is sensitive and carries stigma. Confidentiality is breached only after consulting the EC. NACO pre-test and post-test counselling. Discordant couples addressed. The partner's right to life comes before privacy. Phase I studies only if the drug cannot be tested in healthy people. Audio recording of consent in anti-HIV drug trials (NDCT Rules).
  4. Mental illness: Mental Healthcare Act 2017 definition. Illness does not equal incapacity. LAR consent if incapable, and re-consent when competence returns. Explain how suicidal ideation will be handled. The EC requires justification for any exception (6.8, Table 6.1).
  5. Children, pregnant women, prisoners and employees: assent by age, justification for including pregnant women, and no penalty for refusing in hierarchical settings.

Project proposal: reasons for non-compliance in patients with HIV, with the ethical issues to be resolved

Ph.D. RM 2016
  1. Title and objectives: proportion of patients on antiretroviral therapy who are non-adherent, and the factors associated with it.
  2. Design: cross-sectional analytical study at the ART centre, with in-depth interviews of a purposive sub-sample. See study designs and qualitative research.
  3. Participants and sampling: adults on therapy who meet the eligibility criteria, with sample size based on the expected prevalence of non-adherence.
  4. Tools: pre-tested questionnaire on adherence and its factors, and an interview guide.
  5. Analysis: prevalence with 95% CI, associations by logistic regression, and thematic analysis of interviews.
  6. Ethical issues:
    • Full committee review, because people living with HIV are a vulnerable group.
    • Consent in the local language, in a private room. Refusal does not affect treatment (ICMR 5.3.10).
    • Interviews by someone outside the treating team, to avoid consent under dependence (Declaration of Helsinki para 27).
    • Coded identifiers, no names on forms, and limits of confidentiality explained (2.3).
    • Referral for adherence counselling and support (6.2.11).
    • Community advisory board and a patient representative at the EC where appropriate (2.10.2, 4.3.11).
    • Results shared with the community without identifying individuals.

Ethical issues in a clinical trial of a new NSAID, and how a double-blind crossover controlled trial is done

DM Clinical Immunology and Rheumatology 2001

Ethical issues

  1. Adequate preclinical and earlier clinical data to justify the trial (ICH E6(R3) principle 4.1).
  2. Permission from the Central Licencing Authority and approval from an EC registered under NDCT rule 8.
  3. Registration with CTRI before the first participant.
  4. Informed consent with all essential elements, and audio-video recording for vulnerable participants if it is a new chemical entity.
  5. Comparator: test against the best proven intervention. Placebo only under Declaration of Helsinki para 33. Keep rescue analgesia available, because not giving available rescue medication counts as trial-related injury (rule 41).
  6. SAE reporting within 24 hours. Stop or modify the trial if risks outweigh benefits (Declaration of Helsinki para 18).
  7. Justified inclusion of vulnerable groups, such as pregnant women (ICMR Box 6.3).
  8. Free medical management and compensation (rules 39–40), and insurance.
  9. Confidentiality, conflict of interest declaration, post-trial provisions (para 34), publication of all results.

Double-blind crossover trial

  1. Suitable for a stable chronic condition and a drug with a short-lasting effect, for example osteoarthritis pain.
  2. Randomise each patient to a sequence: new NSAID then comparator, or comparator then new NSAID.
  3. Period 1 → washout long enough for the first drug's effect to disappear → period 2.
  4. Double-blind: identical-looking medicines, codes held by a third party. Neither patient nor assessor knows the treatment.
  5. Each patient is their own control, so fewer patients are needed. Analyse within-patient differences and check for period and carry-over effects.
  6. Not suitable for curable conditions or drugs with lasting effects. See the clinical trials chapter.

Institutional Animal Ethics Committee: members and their responsibilities

MD Pharmacology 2020, 2025
  1. Legal basis: PCA Act 1960 and the Breeding of and Experiments on Animals (Control and Supervision) Rules 1998, registered with CCSEA (formerly CPCSEA).
  2. Members (8): from the establishment, a biological scientist, two scientists from different biological disciplines, a veterinarian (mandatory) and the scientist in charge of the animal facility. From CCSEA, a main nominee, a scientist from outside the institute and a socially aware nominee. A link nominee replaces the main nominee when absent. A specialist may be co-opted for hazardous agents.
  3. Chairperson and Member Secretary are chosen from the five institutional members (six if a non-scientist head of the institution is proposed as Chairperson). Foreign nationals cannot be members.
  4. Tenure: 5 years, with registration. At least half the internal members replaced at reconstitution.
  5. Quorum: 6, with the main nominee present. At least two meetings a year. Minutes sent to CCSEA within 15 days.
  6. Responsibilities: review and approve protocols on small animals before the study, and forward large-animal proposals to CCSEA with a recommendation. Monitor experiments during and after the study and visit the animal house. Ensure compliance with rules and guidelines. Keep records, maintain confidentiality and declare conflicts of interest.
  7. Member Secretary: organises meetings, maintains records, prepares minutes and communicates decisions.

Principles of animal experimentation, and six points from the guidelines on the use of animals in scientific research

Ph.D. RM 2019, 2020

ICMR 2017 (3.2.2) requires researchers to follow the PCA Act 1960, the Breeding and Experimentation Rules 1998 (amended 2001 and 2006), the INSA guidelines, the ICMR Guidelines on Humane Care and Use of Laboratory Animals (2006) and the CPCSEA guidelines. Six points from these rules:

  1. 3Rs (Russell and Burch, 1959): replacement, reduction, refinement.
  2. Choice of animal: the lowest on the phylogenetic scale that gives valid results, and the minimum number for a statistically valid result (rule 9(bb)).
  3. Qualified people: experiments done by or under the supervision of a person qualified in veterinary science, medicine or laboratory animal science (rule 9(a)).
  4. Pain: anaesthesia for procedures more severe than simple inoculation or superficial venesection. An animal in severe pain is painlessly killed without continuing (rule 9(d), (f)).
  5. Care: animals looked after before and after experiments. Aftercare and rehabilitation are the investigator's responsibility (rule 9(c), (cc)).
  6. Approval and sourcing: IAEC approval before the study. Animals from registered breeders (rule 10). No experiments only to gain manual skill, except in recognised training institutions (rule 9(g)).

Publication ethics

Ph.D. RM 2021
  • Authorship by the four ICMJE criteria, with no gift or ghost authors (ICMR 2017, Box 3.3).
  • Publish completed research whatever the result (ICMR 3.4.3, Declaration of Helsinki para 36).
  • No duplicate submission of papers or grant applications (3.6.4).
  • Declare funding, affiliations and conflicts of interest.
  • Protect participant identity, and take re-consent before publishing identifiable photographs (2.3.3).
  • Plagiarism, fabrication, falsification, predatory journals and peer review: see the publishing and IPR chapter.

The one thing to remember

No participant is enrolled until the ethics committee has approved the protocol and the participant has given informed consent.

Compensation examples use made-up participants for teaching. The formula, base amount and factors are from the NDCT Rules 2019, Seventh Schedule.

Sources: Indian Council of Medical Research. National Ethical Guidelines for Biomedical and Health Research Involving Human Participants. New Delhi: ICMR; 2017. ISBN 978-81-910091-94. ICMR. Ethical Guidelines for Biomedical Research on Human Participants. New Delhi: ICMR; 2006. New Drugs and Clinical Trials Rules, 2019. G.S.R. 227(E), Gazette of India, 19 March 2019 (as amended, CDSCO consolidated text). World Medical Association Declaration of Helsinki: ethical principles for medical research involving human participants. JAMA 2025;333(1):71–4 (doi:10.1001/jama.2024.21972; PMID 39425955). World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013;310(20):2191–4 (doi:10.1001/jama.2013.281053; PMID 24141714). Nuremberg Code. Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10, Vol. 2. Washington DC: US Government Printing Office; 1949. Shuster E. Fifty years later: the significance of the Nuremberg Code. N Engl J Med 1997;337(20):1436–40 (doi:10.1056/NEJM199711133372006). National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report. Federal Register, 18 April 1979. Corbie-Smith G. The continuing legacy of the Tuskegee Syphilis Study. Am J Med Sci 1999;317(1):5–8 (doi:10.1097/00000441-199901000-00002). Reverby SM. Ethical failures and history lessons: the U.S. Public Health Service research studies in Tuskegee and Guatemala. Public Health Rev 2012;34(1) (doi:10.1007/BF03391665). ICH E6(R3) Guideline for Good Clinical Practice, Step 4, 6 January 2025. European Medicines Agency, ICH E6 good clinical practice scientific guideline page (effective dates). Russell WMS, Burch RL. The Principles of Humane Experimental Technique. 1959. Flecknell P. Replacement, reduction and refinement. ALTEX 2002;19(2):73–8 (PMID 12098013). Breeding of and Experiments on Animals (Control and Supervision) Rules, 1998, as amended by S.O. 1818(E), 23 October 2006. CCSEA. Standard operating procedures for IAEC (Compendium of CPCSEA). CCSEA letter V-11011(13)/13/2022-CPCSEA-DADF, 6 January 2023. ICMR. Frequently asked questions for Institutional Animal Ethics Committees. 2025.

Past papers

Every TNMGRMU question on research ethics

Each one is answered in this chapter. Tap a sitting to open the university's own question paper.

  1. ×2Ethics of ResearchPh.D. RM · Jan 2025Ph.D. RM · Jul 2014
  2. ×2Declaration of HelsinkiMD Forensic Medicine · Apr 2016MD Pharmacology · Oct 2015
  3. ×2Institutional review boardPh.D. RM · Jan 2016MCh Surgical Oncology · Aug 2009
  4. ×2Modified declaration of HelsinkiMD Pharmacology · Apr 2015MD Pharmacology · Mar 2008
  5. ×1Institutional Animal Ethics Committee Members and their responsibilityMD Pharmacology · May 2025
  6. ×1Good clinical practice in clinical research protocolMD Community Medicine · Oct 2025
  7. ×1Constitution and Procedure for Registration of Institutional Ethics Committee of your Institution Planning to conduct Clinical Trials. Add a note on roles and responsibilities of Member Secretary and Legal ExpertMD Pharmacology · May 2023
  8. ×1Write in detail about ICMR guidelines for Human ResearchMD Forensic Medicine · Oct 2023
  9. ×1Research EthicsPh.D. RM · Jan 2023
  10. ×1Institutional Ethics Committee and its rolesMD Pharmacology · Nov 2021
  11. ×1Ethical considerations in Experimental studies involving human beingsPh.D. RM · Aug 2021
  12. ×1Publication EthicsPh.D. RM · Aug 2021
  13. ×1Institutional animal ethics committeeMD Pharmacology · Aug 2020
  14. ×1Give six points on ICMR guidelines on the use of animals in Scientific ResearchPh.D. RM · Dec 2020
  15. ×1Explain “Compensation of Participation” in Clinical TrialsPh.D. RM · Dec 2020
  16. ×1Role of Institutional Ethics Committee in researchMD Pharmacology · May 2019
  17. ×1Briefly explain the principles involved in conducting animal experimentsPh.D. RM · Jan 2019
  18. ×1Describe the principles in compensation for participation in clinical trialsPh.D. RM · Jan 2019
  19. ×1(a) Outline the key components of Research Protocol. (b) Discuss ethical issues on Research involving HIV +ve, mentally ill patients and other vulnerable groupsPh.D. RM · Jul 2019
  20. ×1Lay person in ethics committeeMD Pharmacology · Oct 2018
  21. ×1What is scientific research and write in brief about ethics involved?Ph.D. RM · Jul 2017
  22. ×1Institutional Ethics CommitteeMD Pharmacology · Oct 2016
  23. ×1You are interested in identifying the reasons for and factors influencing non-compliance in the patients diagnosed to be HIV +ve. Write a detailed project proposal highlighting the research design including the ethical consensus to be solvedPh.D. RM · Jan 2016
  24. ×1ICMR guidelines for ethicsPh.D. RM · Jan 2016
  25. ×1Ethical principlesPh.D. RM · Jul 2016
  26. ×1ICMR Ethical guidelinesPh.D. RM · Jan 2015
  27. ×1Good clinical practiceMD Pharmacology · Oct 2014
  28. ×1Need for research ethicsPh.D. RM · Jan 2014
  29. ×1Human ethics committee function and organizationMD Pharmacology · Oct 2013
  30. ×1Enumerate the Principles, laid down by ICMR that is to be followed when using human beings for research. Give the details pertaining to Principles of Informed Consent and the Principles of CompetencePh.D. RM · Jul 2013
  31. ×1Discuss the major ethical issues that must be addressed in devising a clinical drug trial of a new NSAID (non steroidal anti inflammatory drug) in human subjects. How is a double blind cross over controlled trial done? (25)DM Clinical Immunology and Rheumatology · Apr 2001