Composition, Responsibilities, Procedures Of IRB/IEC

🧬 Composition, Responsibilities, and Procedures of IRB / IEC

🔷 Introduction

An IRB (Institutional Review Board) or IEC (Independent Ethics Committee) is an independent regulatory body responsible for the ethical review, approval, and monitoring of research involving human subjects.

🎯 Main Objective

To ensure that all research involving humans is conducted in accordance with ethical principles, and that the rights, safety, and well-being of participants are protected.

🔷 Composition of IRB / IEC

An IRB/IEC should consist of a reasonable number of members who collectively have the scientific, medical, and ethical expertise to review clinical research.

Recommended composition (ICH-GCP & ICMR aligned):

• Minimum 5 members
• Multidisciplinary and multisectoral
• Scientific members (medicine, pharmacy, research background)
• At least one non-scientific member (ethicist, lawyer, social worker, lay person)
• At least one independent member (not affiliated with the institution/trial site)
• Gender representation
• Lay person to represent community perspective

➡️ A quorum is mandatory for decision-making.

🔷 Core Responsibilities of IRB / IEC

✅ 1. Protection of Human Subjects

• Safeguard the rights, safety, and well-being of all trial subjects
• Give special attention to vulnerable populations, such as:
• Children
• Pregnant women
• Elderly
• Economically or socially disadvantaged groups
• Prisoners

✅ 2. Review of Essential Documents

Before approving a trial, the IRB/IEC must review:

1.     Trial protocol(s)

2.     Written informed consent form(s)

3.     Subject recruitment procedures and materials

4.     Written information to be provided to subjects

5.     Investigator’s Brochure (IB)

6.     Information on payment and compensation

7.     Available safety information

8.     Investigator’s current CV or proof of qualifications

✅ 3. Review and Decision-Making

The IRB/IEC must review clinical trial proposals within a reasonable time and document its decisions in writing, clearly identifying:

• Trial details
• Documents reviewed
• Date of review
• Decision taken

Possible decisions include:

• ✔ Approval / favorable opinion
• 🔄 Modifications required before approval
• ❌ Disapproval / negative opinion
• ⛔ Suspension or termination of prior approval

✅ 4. Assessment of Investigator Qualifications

• Review investigator’s education, training, and experience
• Based on curriculum vitae and supporting documents
• Ensure the investigator is qualified to conduct the study safely

✅ 5. Continuing Review of Ongoing Trials

• Conduct continuing review of all approved trials
• Frequency depends on risk level
• At least once per year
• More frequent review for high-risk studies

✅ 6. Review of Subject Information

• The IRB/IEC may request additional information to be provided to subjects
• When it improves:
• Understanding
• Safety
• Protection of rights
• Decision-making capacity

✅ 7. Review of Payment and Compensation

• Ensure payments are:
• Not coercive
• Free from undue influence
• Verify that payment details are clearly mentioned in the informed consent form
• Payment should be fair and preferably pro-rated

🔷 Procedures of IRB / IEC

The IRB/IEC must function according to written Standard Operating Procedures (SOPs).

Key procedures include:

• Defining IRB/IEC composition and authority
• Scheduling and conducting formal meetings
• Ensuring quorum before decisions
• Performing initial and continuing review
• Allowing expedited review for minor changes
• Ensuring no subject is enrolled without written approval
• Requiring prior approval for protocol changes, except to eliminate immediate hazards
• Ensuring investigators promptly report:
• Protocol deviations
• Serious and unexpected adverse drug reactions
• Risk-increasing changes
• New safety information

The IRB/IEC must inform investigators in writing about:

• Decisions and opinions
• Reasons for decisions
• Appeal procedures

🔷 Conclusion

The IRB/IEC plays a central role in ethical clinical research. Through independent review, continuous monitoring, and strict adherence to ethical and regulatory standards, it ensures that human dignity, safety, and rights remain the highest priority in clinical trials.

Informed Consent Process

 

✅ INFORMED CONSENT PROCESS (ICP)

📘 Definition (ICH-GCP Based)

The informed consent process is a continuous, interactive process by which a subject voluntarily confirms willingness to participate in a clinical study after being fully informed of all aspects of the trial that are relevant to the decision to participate.

➡️ It is documented by a written, signed, and dated Informed Consent Form (ICF).

📗 Introduction – Key Concepts

Informed consent is not just signing a form, it is about:

1. ✔️ Understanding the study
2. ✔️ Voluntary decision-making
3. ✔️ Ongoing communication

Important points:

• The consent document is essential, but discussion with a knowledgeable research team member is equally important.
• Investigators must educate, not merely disclose information.
• Subjects should be allowed to ask questions at any time — before, during, and after the trial.
• Therefore, informed consent is an ongoing interactive process, not a one-time event.

📙 Objectives of Informed Consent

• To protect the rights, safety, and well-being of subjects
• To ensure voluntary participation
• To promote ethical and transparent research
• To support autonomous decision-making

📕 Essential Steps in the Informed Consent Process

🔹 1. Obtaining informed consent from every subject

• Mandatory in all clinical studies
• No subject can be enrolled without consent (except approved emergency exceptions).

🔹 2. Consent must be obtained before trial participation

• Before:
• Screening procedures
• Sample collection
• Any trial-related activity

🔹 3. Subject must sign the consent form

• Consent must be:
• Written
• Signed
• Personally dated
• Confirms voluntary agreement.

🔹 4. Legally Acceptable Representative (LAR)

If the subject:

• Cannot write
• Cannot understand
• Is from a vulnerable population (e.g., children, cognitively impaired, unconscious)

➡️ Then consent must be taken from the Legally Acceptable Representative (LAR).

Examples:

• Parent / guardian (children)
• Court-appointed guardian
• Authorized caregiver (as per law)

🔹 5. Investigator’s responsibilities

The person obtaining consent must:

• Be qualified and trained
• Clearly explain:
• Purpose of the study
• Procedures
• Risks and benefits
• Alternatives
• Confidentiality
• Compensation and injury policy
• Right to withdraw

The following must sign and personally date the consent form:

• ✔️ Study subject / LAR
• ✔️ Investigator (or authorized designee)
• ✔️ Impartial witness (if applicable)

🔹 6. Role of Impartial Witness

Required when:

• Subject/LAR cannot read
• Subject is illiterate

The impartial witness must:

• Be independent of the study
• Be present during the entire consent discussion
• Ensure there is no coercion or undue influence

The relationship of the witness to:

• Subject
• [1]Investigator
• Study
  ➡️ must be documented

📒 Witness Attestation

After:

• Information is read and explained
• Subject/LAR gives oral consent
• Subject/LAR signs the ICF

➡️ The witness must sign and date the form.

By signing, the witness confirms that:

• Information was accurately explained
• It was apparently understood
• Consent was freely given

📓 Key Features of a Proper Informed Consent Process

• 🔁 Ongoing, not one-time
• 🗣️ Two-way communication
• 🧠 Focus on understanding
• 🚫 Free from force, pressure, or manipulation
• 📄 Properly documented

📔 Simple Flow

1. Identify eligible subject
2. Provide Participant Information Sheet
3. Explain study in understandable language
4. Allow time for questions
5. Confirm understanding
6. Obtain voluntary agreement
7. Signatures & dates
8. Give copy to subject
9. Continue consent discussions throughout study

🎯 Exam-Oriented Points

• Informed consent = process + document
• Must be obtained before any trial procedure
• Must be voluntary, informed, documented
• LAR signs when subject is incapable
• Impartial witness required for illiterate subjects
• Investigator must be qualified
• ICP is an ongoing ethical obligation

🧾 One-Line Summary for Students

“Informed consent is a continuous ethical and legal process that ensures a subject’s voluntary participation in research after fully understanding all relevant aspects of the study.”

 

✅ Steps in Obtaining the Informed Consent

Obtaining informed consent is a systematic, ethical, and documented process. It must ensure that the subject understands the study and participates voluntarily, without any pressure.

🧭 Step-by-Step Informed Consent Procedure

🔹 1. IRB / IEC Approval

• Obtain prior approval of the informed consent document from the Institutional Review Board (IRB) / Independent Ethics Committee (IEC).
• Only the approved version of the consent form may be used.
• Any modification requires re-approval before use.

➡️ No consent process is valid without ethics committee approval.

🔹 2. Provide the Consent Document

• Present the Participant Information Sheet / Informed Consent Form (ICF) to the prospective subject.
• Language must be:
• Simple
• Non-technical
• Understandable to the subject.

🔹 3. Explain the Study Clearly

The investigator (or authorized trained person) must explain:

• Purpose of the research
• Study procedures
• Duration of participation
• Responsibilities of the subject

Information must be given in a neutral, non-coercive manner.

🔹 4. Encourage Questions and Discussion

The subject must be prompted to ask questions.

Mandatory discussion includes:

• ✔️ Risks and discomforts
• ✔️ Expected benefits
• ✔️ Alternative treatments or procedures
• ✔️ Confidentiality
• ✔️ Compensation and injury management
• ✔️ Right to refuse or withdraw at any time

➡️ All questions must be answered honestly and completely.

🔹 5. Provide a Copy of the Consent Form

• Give the subject a copy of the consent document.
• Allow them to read it fully at their own pace.

🔹 6. Allow Adequate Decision-Making Time

• Subject must be given enough time to:
• Think
• Discuss with family/friends
• Consult their physician if desired

➡️ No rushing, no pressure, no inducement.

🔹 7. Assess Understanding

At a follow-up meeting, the investigator should ask open-ended questions, such as:

• “Can you explain what this study is about?”
• “What are the possible risks?”
• “What are your rights if you join this study?”

This step confirms that the subject has correctly understood:

• Nature of the study
• Procedures
• Risks and benefits
• Voluntary nature of participation

🔹 8. Obtain Voluntary Signature

If the subject:

• Demonstrates adequate understanding
• Freely agrees to participate

➡️ The subject signs and personally dates the informed consent form.

Also required (as applicable):

• Investigator’s signature
• Legally acceptable representative
• Impartial witness (if subject is illiterate)

A signed copy must be given to the subject.

🔁 Important Emphasis

• Informed consent is a process, not an event.
• Understanding is more important than documentation.
• Consent must be re-confirmed when:
• New risks emerge
• Protocol changes occur
• Long-term studies continue.

🧠 Flowchart for Students

IRB Approval
⬇️
Provide ICF
⬇️
Explain study
⬇️
Encourage questions
⬇️
Give copy of ICF
⬇️
Allow decision time
⬇️
Assess understanding
⬇️
Voluntary signature
⬇️
Continuous consent process

🎯 Exam-Oriented Key Points

• Ethics committee approval is mandatory before consent
• Risks, benefits, and alternatives must always be explained
• Adequate time must be given for decision-making
• Understanding must be assessed using open-ended questions
• Consent must be voluntary, informed, and documented

📝 One-Line Summary for Blog/Notes

“Obtaining informed consent involves ethics approval, clear explanation, opportunity for questions, assessment of understanding, and voluntary documentation, ensuring ethical participation in clinical research.”

 

✅ SPECIAL CONSIDERATIONS IN INFORMED CONSENT

Certain populations require additional ethical protections because they may have limited ability to understand or decide independently. The most important among them are:

• Children
• Incompetent individuals

🧒 INFORMED CONSENT IN CHILDREN (PEDIATRIC SUBJECTS)

Children are considered a vulnerable population because they usually cannot legally provide valid informed consent.

🔹 Key Ethical Principles

When children are involved in research:

• The study must be ethically justified
• Specific benefits of participation must be clearly explained
• Possible discomforts and risks must be honestly described
• The child’s welfare always takes priority over research goals

🔹 Parental Permission

• Parental/guardian consent is mandatory for all research involving children.
• Depending on the risk level, consent is required from:

✔️ One parent is sufficient when:

• The study involves minimal risk, or
• The study offers a direct potential benefit to the child.

✔️ Both parents are required when:

• The study involves more than minimal risk,
• And no direct benefit is expected for the child.

🔹 Child’s Assent

In addition to parental consent, the child’s assent must be obtained whenever the child is capable of understanding.

🔸 What is assent?

Assent means the child affirmatively agrees to participate in the research.

It is:

• Not legally binding consent
• But an ethical requirement

🔹 Age and Understanding

• Typically, children above 7 years of age are considered capable of giving assent.
• Assent should be obtained using a separate, age-appropriate assent form.
• The explanation must be:
• Simple
• Non-threatening
• Suitable for the child’s level of understanding.

🔹 Important Teaching Point

Even if parents consent, a child’s objection should be respected, unless the study offers a life-saving or essential therapeutic benefit.

🧠 INFORMED CONSENT IN INCOMPETENT INDIVIDUALS

This group includes people who cannot adequately understand or communicate decisions, such as:

• Individuals with severe mental disability
• Patients with advanced dementia
• Unconscious or delirious patients
• Elderly persons with major sensory or cognitive impairment

🔹 Use of a Proxy / Legally Acceptable Representative (LAR)

When a subject is incompetent:

➡️ Consent must be obtained from a Legally Acceptable Representative (proxy).

Examples:

• Court-appointed guardian
• Legal caregiver
• Authorized family member (as per law)

🔹 Responsibilities of the Proxy

The proxy must:

·        Act in the best interest of the subject

·        Discuss the decision with:

• Family members
• Treating physicians
• Caregivers

·        Ensure that the decision reflects what the subject would have chosen if competent (substituted judgment principle).

🔹 Investigator’s Ethical Duties

The investigator must ensure that:

• The research is necessary for this population
• Risks are minimized
• Rights and dignity are fully protected
• The subject is involved as much as possible in the discussion, even if full consent cannot be given.

📌 Quick Comparison Table (For Teaching & Blog)

Aspect	Children	Incompetent Individuals
Parental/LAR consent	Mandatory	Mandatory
Assent	Required when capable (>7 yrs)	Seek subject’s opinion if possible
Risk protection	Very strict	Very strict
Ethical basis	Best interest + developing autonomy	Best interest + substituted judgment

🎯 Exam-Oriented Key Points

• Children and incompetent persons are vulnerable populations
• Parental consent is compulsory for children
• Assent is an ethical requirement, not legal consent
• Both parents are required when risk > minimal without benefit
• In incompetent subjects, consent must be taken from a legally acceptable representative
• Decisions must reflect what the subject would choose if competent

📝 One-Line Summary

“Special populations such as children and incompetent individuals require enhanced informed consent procedures involving parental or proxy permission, along with assent whenever possible, to ensure ethical and lawful participation in research.”

 

✅ INFORMED CONSENT IN EMERGENCY SITUATIONS

Emergency situations present unique ethical challenges because the subject’s life may be at immediate risk, and there may be no time or ability to obtain standard informed consent.

Most clinical research regulations (ICH-GCP, national drug rules, and ethics guidelines) therefore allow a limited emergency exception to informed consent — under strictly controlled conditions.

📌 What is Emergency Use?

Emergency use refers to the use of an investigational product in a life-threatening situation where:

• Immediate intervention is required
• The subject is unable to give consent
• A legally acceptable representative (LAR) is not available in time

🧭 Core Ethical Principle

Even in emergencies, the guiding principles remain:

• Protection of life
• Respect for human rights
• Independent medical judgment
• Strict documentation and review

Emergency use is an exception, not a routine practice.

📝 Regulatory Requirements Before Emergency Use

If an investigator determines that there is not enough time to obtain informed consent from the subject or LAR, the following steps are mandatory:

🔹 1. Independent Medical Review

• The investigator’s decision must be reviewed by another physician
• This physician must be:
• Qualified
• Independent
• Not part of the clinical study team

➡️ This protects against bias and misuse.

🔹 2. Written Certification Must Be Obtained

Before using the investigational product, the investigator must document written certification confirming all of the following:

✔️ (1) Life-threatening situation

The subject is facing a life-threatening or severely debilitating condition requiring immediate intervention.

✔️ (2) Inability to obtain subject consent

• The subject is unable to communicate
• Or is unconscious/incapacitated

Therefore, informed consent cannot be obtained directly.

✔️ (3) Insufficient time to obtain LAR consent

There is not enough time to locate and obtain consent from the legally acceptable representative before treatment must begin.

✔️ (4) No satisfactory alternative therapy

There is no generally accepted standard therapy that offers an equal or greater likelihood of saving the subject’s life.

🔁 After the Emergency Intervention

As soon as possible:

• Inform the subject (if recovered)
• Or inform the legally acceptable representative
• Obtain formal informed consent for:
• Continuation in the study
• Use of collected data
• Report the emergency use to:
• Ethics Committee / IRB
• Sponsor (as required)

⚠️ Important Points

• Emergency consent waiver is temporary and situation-specific
• It does not remove the need for consent, it only delays it
• Independent physician review is mandatory
• Full documentation is legally critical
• Ethics committee oversight must follow

🧠 Simple Flow (For Students)

Life-threatening emergency
⬇️
No time + subject incapacitated
⬇️
Independent physician review
⬇️
Written certification (4 conditions)
⬇️
Emergency use of investigational product
⬇️
Inform subject/LAR ASAP
⬇️
Obtain formal consent + notify IRB

🎯 Exam-Oriented Key Points

• Emergency use is allowed only in life-threatening situations
• Independent physician confirmation is required
• Four written certifications are mandatory
• No equally effective standard therapy must exist
• Post-emergency consent and ethics reporting are compulsory

📝 One-Line Summary for Notes/Blog

“In emergency situations where life is threatened and consent cannot be obtained, investigational products may be used only after independent medical review, strict written certification, and subsequent ethics committee reporting.”

 

 

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