UNIT IV

Drug Regulatory Affairs

 Clinical Trials

• Clinical trial is a systematic investigation in human subjects for evaluating the safety
& efficacy of any new drug.
• Clinical trials are a set of tests in medical research and drug development that
generate safety and efficacy data for health interventions in human beings.
 Need for Clinical Trials

• Research studies involving people

• Try to answer scientific questions and find better ways to prevent, diagnose, or treat
disease
• Translate results of basic scientific research into better ways to prevent, diagnose, or
treat disease
Time Line for Drug Development Process
Different Phases of Clinical Trials
 Clinical Trial Protocol

• Title Page
• Signature Page
• Content Page
• List of Abbreviations
• Introduction/Abstract
• Objectives
• Background/Rationale
• Eligibility criteria
• Study design
• Safety/ Adverse event
• Regulatory Guidance
• Statistical Section (Including analysis and monitoring)
• Human Subjects Protection/ Informed consent form
 Institutional Review Board/ Independent Ethics
Committee

• IRB/IEC serves as an independent body that reviews, evaluates, approves and

decides on the scientific and ethical aspects of the clinical trial protocol as well as
the benefits and risks to the study participants
• Main purpose of IRB/IEC is to protect the rights, safety, and well-being of the
subjects who participate in a trial
 Composition of IRB/IEC

• Consists of members, who collectively have the qualifications and experience to

review and evaluate the science, medical aspects, and ethics of the proposed trials
• Includes at least five members, of which at least one member whose primary area of
interest is non scientific, and at least one member who is independent of the
institution/trial site
 Responsibilities of IRB/IEC

• Safeguard the rights, safety, and well-being of all trial subjects

• Reviews a proposed clinical trial within a reasonable time and document its views in
writing
• Conducts continuing review of each ongoing trial at least once per year
• Ensures that information regarding payment to subjects (including the methods,
amounts, schedule of payment) is set forth in the written informed consent form and
any other written information is provided to the subjects
 Procedures of IRB/IEC

• Determines its composition and authority under which it is established

• Schedules, notifies its members of, and conducts its meetings
• Conducts initial and continuing review of trials
• Specifies that no subject should be admitted to a trial before the IRB/IEC issues its
written approval/favourable opinion of the trial
• Specifies the information that the investigator should promptly report to the IRB/IEC
(like deviations from the protocol, adverse drug reactions etc.)
 Maintenance of Records of IRB/IEC

• IRB/IEC retains all relevant records (e.g., written procedures, lists of occupations/
affiliations of members, submitted documents, minutes of meetings, etc.) for a
period of at least 3 years after completion of the trial and makes them available upon
request from the regulatory authority.
• IRB/IEC may be asked by investigators, sponsors, or regulatory authorities to
provide copies of its written procedures and membership lists
 Formulation and Working Procedures Informed Consent
Process and Procedures

• Definition as per International Conference on Harmonization E6 - Good

Clinical Practice :
– A process by which a subject voluntarily confirms his or her willingness to
participate in a participate in a particular trial, after having been having been
informed of all aspects of the trial that are relevant to the subject’s decision to
decision to participate. Informed consent is documented by means of a means of a
written, signed and dated informed informed consent form.”
Informed Consent Process
Conceptual Framework-Informed Consent Process
 Required Components of ICF (ICMR Guideline, 2006)

• Nature and purpose of study stating it as research

• Duration of participation with number of participants
• Procedures to be followed
• Investigations, if any, to be performed
• Foreseeable risks and discomforts adequately described and whether project involves
more than minimal risk
• Benefits to participant, community or medical profession as may be applicable
• Alternative treatments, if available
• Steps taken for ensuring confidentiality
• Policy on compensation
 Required Components of ICF (ICMR Guideline, 2006)

• Availability of medical treatment for such injuries or risk management

• No loss of benefits on withdrawal
• Benefit sharing in the event of commercialization
• Contact details of PI or local PI/Co-PI in multi centric studies for asking more
information
• Contact details of Chairman of the IEC for appeal against violation of rights
• Voluntary participation
• If test for genetics and HIV is to be done, counselling for consent for testing must be
given as per national guidelines
• Storage period of biological sample and related data with choice offered to
participant regarding future use of sample, refusal for storage and receipt of its
results
 Informed Consent - Schedule Y

• In all trials, a freely given, informed, written consent is required to be obtained from
each study subject.
• The Subject’s consent must be obtained in writing using an ‘Informed Consent
Form’.
• Both the PIS and the ICF should be approved by the ethics committee and furnished
to the Licensing Authority.
• Where a subject is not able to give informed consent, it may be obtained from a
legally acceptable representative. An impartial witness should be present if LAR is
illiterate.
• A checklist of essential elements given in Appendix V
 Assent

• Assent’ means a child's affirmative agreement to participate in research.

• “All paediatric participants should be informed to the fullest extent possible about
the study in a language and in terms that they are able to understand.” – Schedule Y
 Community Consent

• Community consent is generally obtained through a process of dialogue with the

community leadership.
• Agreement from the community leadership is obtained prior to, but does not replace,
the consent and/or assent of individual participants.
 HIPAA

• HIPPA is the Health Insurance Portability and Accountability Act of 1996.

• It is a Privacy rule provides Federal Privacy Protection for individually identifiable
health information called Protected Health Information
 Contents of HIPAA

• Title 1-Protects Health Insurance Coverage for workers and their families when they
change or lose their job.
• Title 2- Prevents Health care Frauds and Abuse.
• Title 3- Guidelines for Pre-Tax medical spending.
• Title 4- Guidelines for Group Health Insurance Plans.
• Title 5 - Governs company owned Life Insurance policies.
 HIPAA Basics

• Covered Entities
• It safeguard all patient data of any form. Excluding some areas, the protected health
information comprises of personal health data sent in any form
• Health plans,
• Healthcare clearinghouses
• Health care providers doctors, nurses, and therapists.
 HIPAA Basics

• Protected Health Information (PHI)

• HIPAA protects all patient information whether it is verbal, written or electronic.
• It includes all individually identifiable health information that is transmitted or
maintained in any form or medium.
• It includes demographic information that ties the identity of the individual to his or
her health record.
• E.g. names, addresses, geographic codes smaller than state, all dates (except year)
elements related to the person, telephone numbers, fax numbers, license numbers,
social security numbers, etc.
 Pharmacovigilance

• Pharmacovigilance is majorly known as drug safety. It is a main integral

part of clinical research. Throughout the product life cycle clinical trials
safety and post marketing pharmacovigilance plays a critical role .
• The word pharmacovigilance is derived from two words one Parmakon is a
Greek word which means “drug” and another vigilare is a Latin word which
means to keep awake or to keep watch.”

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 Pharmacovigilance

• Pharmacovigilance is “defined as the pharmacological science relating to the

detection, understanding, assessment and prevention of adverse effects, particularly
long term and short term adverse effects of medicines” .
• According to WHO Pharmacovigilance (PV) is the pharmacological science relating
to the detection, evaluation, understanding and prevention of adverse effects,
especially long term and short term side effects of medicines .

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 Aims of Pharmacovigilance

• To improve patient care & safety

• To contribute to assessment of benefit, harm & effectiveness of medicine
• To Identify previously unrecognized adverse effects of the drugs
• To Promote rational & safe use of medicine
• To Promote education & clinical training
• To Identify patient related risk factors of ADR such as dose, age, gender
• Any response to a drug which is unintended , occurs at particular doses
• To diagnose or therapy of disease, or for the modification, of physiological
function.

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 Adverse Drug Reactions

• ADR is a response to drug, which alters the normal physiological function of the
body, factors which causes ADR includes mainly multiple drug therapy, age &
gender.
• They are mainly two types of ADR
– TYPE A: These are common, predictable, dose dependent, they are seldom fatal
– TYPE B: These are uncommon, unpredictable, dose independent; they involve
relatively high rates of serious morbidity.

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 Post Marketing Surveillance

• Pharmaceutical drug or medical device is monitored often after it has been

released in to the market, Since drugs are approved based of clinical trials
which involve relatively small number of people who do not have any other
medical complications, post marketing surveillance play an important role
to know the ADRs of drugs after they have released in to the market.
• Approaches by
– spontaneous ADR reporting
– Prescription event monitoring
– Electronic health records
– Patient Registers

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Pharmacovigilance Frame Work

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 Pharmacovigilance Programme of India (PVPI)

• It officially starts on 23rd November 2004 at New Delhi, is under the

control of CDSCO (Central Drug Standard Control Organization),
Directorate general of health services, Indian pharmacopeia commission
(Ghaziabad). The program is conducting by NCC (National Coordinating
Centre) to ensure that the benefits of use of medicine against the risks.
• Objectives
– To monitor ADRs
– To create awareness among health care professionals about ADRs
– To monitor benefit-risk profile of medicines
– Support the CDSCO

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 Summary

• Protocols of the clinical trials were learnt along with the various phases of the
clinical trials. Importance of the institutional review board were discussed along
with HIPPA.
• Pharmacovigilance gives information to assess the safety profile of a drug; the
success of pharmacovigilance is largely dependent on the participation of
professionals of health care countrywide to report ADRs/AEs,

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