LEGALLY

AUTHORIZED REPRESENTATIVE
(LAR) IN CLINICAL TRIALS

Nirmal Kumar Yadav

Pharm D Intern
Clinical Research
Fortis Escort Heart Institute, Okhla
Definition of Legally Acceptable Representative (LAR)

Legal Why LAR is 3

Types of
1 2
Representative necessary Representatives

An individual or LARs help people In clinical research,

juridical or other body who can’t make LARs include Legal
authorized under decisions for guardians,
applicable law to themselves, making Healthcare proxies,
consent, on behalf of a sure they stay safe, Power of Attorney
prospective subject, to get the care they need, (POA) holders, Next
the subject's and can take part in of Kin, and
participation in the important medical Institutional
clinical trial. research. Representatives.
Importance of Legally Acceptable Representative

Protecting Rights Ensures Ethical Conduct Ensuring Fairness

LARs play a vital role By providing informed LARs help mitigate risks
in ensuring that the consent through an associated with
rights and safety of authorized exploitation or coercion by
participants are upheld representative, clinical ensuring that consent is
throughout the research trials can maintain obtained ethically and
process. They help ethical standards and transparently.
ensure that participants uphold the integrity of
are treated ethically and the research process.
with respect.
Historical Evolution of LAR
19th Century No formal consent, vulnerable populations unprotected
1900 Berlin Code
1964 Declaration of Helsinki
1974 U.S. National Research Act
1996 ICH-GCP Guidelines
2001-2004 EU Clinical Trial Directive
2018 GDPR Regulations
2020 ICH-GCP Guidelines
2001-2004 Present: Digital & AI-Based LAR Consent
Ancient Times - 19th Century
(No formal consent, vulnerable populations unprotected)
1900: Berlin Code (Germany)
(First legal attempt to regulate informed consent)
1947: Nuremberg Code
(Introduced voluntary consent but no LAR concept)
1964: Declaration of Helsinki
(Recognized proxy consent for vulnerable populations)
1974: U.S. National Research Act
(Established IRBs, allowed LAR for informed consent)
1996: ICH-GCP Guidelines
(Clear definition of LAR in global clinical trials)
2001-2004: EU Clinical Trials Directive
(Standardized LAR role across Europe)
2018: GDPR Regulations
(Strengthened consent documentation for LARs)
2020s-Present: Digital & AI-Based LAR Consent
(e-Consent, stricter ethics regulations, global harmonization)
 Ethical Considerations
Autonomy Beneficence Justice Patient Safety

• Respecting • Acting in their • Fairness in • Researchers

individual best interest. research must avoid
choices • LARs make • Everyone causing harm
Some people sure that should have a to participants.
can’t make joining a fair chance to • By involving
medical clinical trial participate in LARs, trials
decisions on can be helpful medical can better
their own. and doesn’t research, assess risks and
LARs help put the person including benefits for
ensure their at unnecessary vulnerable those unable to
rights and risk. people. LARs consent
choices are help prevent independently
respected. discrimination
or exclusion.
Structure of Legally Acceptable Representative

Authorization and Communication and

1 2 Legal Standing 3
Consent Advocacy

Representative requires Representative must have Effective representative

the authorization and the legal standing to act involves clear
consent of the represented on behalf of their clients, communication, advocacy
party, establishing a legal ensuring they are duly for the client's interests,
relationship between the authorized and competent and diligent
representative and the to represent them. representative in legal
client. proceedings.
 Regulatory Guidelines

• ICH-GCP: ICH-GCP guidelines highlight the role of Legally Acceptable Representatives (LARs) in
ensuring informed consent, safeguarding participants' rights, and promoting welfare in clinical
trials. ICH-GCP follows the Declaration of Helsinki

• FDA: The FDA allows an LAR to provide informed consent on behalf of individuals unable to consent
due to medical or cognitive conditions. The LAR must be legally recognized under applicable laws
and ensure participant rights, safety, and welfare during clinical trials. The FDA follows the U.S.
Department of Health and Human Services (HHS) regulations, specifically 21 CFR 50 (Protection
of Human Subjects)
Regulatory Guidelines

• EMA: The European Medicines Agency (EMA) has established regulations for involving Legally
Authorized Representatives (LARs) in obtaining informed consent for clinical trials. These
regulations ensure that ethical standards are upheld across all EU member states to protect
participants' rights and welfare. The European Medicines Agency (EMA) follows the EU
Clinical Trial Regulation (CTR) No. 536/2014

• WHO: The World Health Organization (WHO) mandates that ethical approval must be obtained
before involving Legally Authorized Representatives (LARs) in clinical trials. This ensures
oversight, compliance with ethical standards, and protection of participants' rights in research. WHO
follows the "Ethical Principles for Medical Research Involving Human Subjects " (DOH).
Indian Regulations (DCGI, ICMR Guidelines)

• DCGI (Drugs Controller General of India):

• The DCGI mandates that ethics committee approval is required for LAR consent
in clinical trials. This ensures that the rights and welfare of participants
are safeguarded, especially when they are unable to consent for themselves.
• ICMR (Indian Council of Medical Research):
• The ICMR defines an LAR as a family member or legal guardian who can provide
consent on behalf of individuals unable to do so due to various reasons, such as
age or mental incapacity.
• ICMR guidelines specify who qualifies as an LAR in India, emphasizing the need for
ethical considerations in research involving vulnerable populations.
Who Can Be an LAR?
• Eligible Individuals:
• Spouse: A legally married partner can act as an LAR.
• Parents or Legal Guardians: For minors or individuals under guardianship, parents or
legal guardians are authorized to provide consent.
• Close Relatives: Siblings, children, or other close relatives may serve as LARs if no
higher-ranking surrogate is available.
• Legally Appointed Representatives: This includes court-appointed individuals who
have the authority to make decisions on behalf of another person.
• Ethics Committee Involvement:
• In complex cases where multiple potential LARs exist, the ethics committee may
decide who is most appropriate to act as the LAR.
Responsibilities of an LAR
• Understanding Trial Details and Risks:
• The LAR must be well-informed about the clinical trial's purpose, procedures, risks,
and potential benefits to make an informed decision on behalf of the participant.
• Providing Informed Consent:
• The primary responsibility of an LAR is to provide informed consent that reflects
the best interests of the participant. This includes ensuring that consent is given
voluntarily and without coercion(Pressuring a participant).
• Ensuring the Participant's Best Interest:
• The LAR must always prioritize the participant's well-being and safety throughout
the research process.
• Monitoring Participant's Condition:
• The LAR should stay informed about the participant's health status and be prepared
to withdraw consent if necessary.
Informed Consent Process & LAR's Role
• Step 1: Investigator explains the study, including
its purpose, risks, and benefits to the LAR.

• Step 2: The LAR reviews all provided information

carefully to ensure understanding.

• Step 3: If needed, the LAR consults with family

members or medical professionals for additional
insights before making a decision.

• Step 4: The LAR signs the informed consent form,

indicating their agreement for the participant to join the
study.
Situations Requiring LAR Consent

• Unconscious or Critically Ill Patients: In cases such as those in intensive care units (ICUs) or

comas where patients cannot communicate their wishes.

• Mentally Incapacitated Individuals: This includes individuals with conditions like Alzheimer's

disease or severe psychiatric disorders who cannot provide informed consent.

• Minors: For participants below the legal age of consent, parental or guardian consent is

necessary.

• Individuals with Cognitive Impairments: Those with intellectual disabilities or other cognitive

impairments may require an LAR to provide consent on their behalf.

Role of Ethics Committees in Approving LAR Consent

• Review and Approve LAR Qualifications: Assess the suitability and eligibility of
potential LARs to act in the best interest of the participant.

• Ensure Voluntary and Informed Decision-Making: Verify that the LAR

understands the study details, risks, and benefits, and that consent is given freely
and without coercion.

• Monitor Compliance with Ethical and Legal Standards: Continuously oversee

adherence to ethical principles, regulatory requirements, and institutional policies
throughout the research.
Best Practices for Ensuring Ethical and Legal Compliance

• Proper Documentation of LAR Consent: Maintain detailed records of the consent

process, including all relevant communications and signed forms.

• Transparent Communication with LAR: Provide clear and ongoing updates about the
study, participant's progress, and any new information that may affect the LAR's decision.

• Training Researchers on LAR Guidelines: Educate research staff about ethical

considerations, regulatory requirements, and best practices related to LARs.

• Ensuring LAR Understands Their Rights and Responsibilities: Clearly outline the LAR's
role, decision-making authority, and the importance of acting in the participant's best
interest.
Conclusion & Summary

• LAR Plays a Critical Role: LARs are essential in safeguarding the rights and welfare
of vulnerable participants in clinical trials.

• Ethical and Legal Compliance is Essential: Proper adherence to ethical principles,

regulatory standards, and institutional policies is necessary for valid consent.

• Regulations Vary Globally: LAR regulations differ across countries, but all share a
common goal of protecting participants and upholding research integrity.

• Training and Oversight Improve Research: Proper training, oversight, and

documentation enhance the ethical and legal integrity of LAR-based research.
References
• International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use. (2023). ICH E6(R2) Good Clinical Practice.

• U.S. Food and Drug Administration. (2023). Code of Federal Regulations Title 21.

• National Commission for the Protection of Human Subjects of Biomedical and

Behavioral Research. (1979). The Belmont Report.

• World Medical Association. (2023). Declaration of Helsinki – Ethical Principles

for Medical Research Involving Human Subjects.
THANK YOU