Good clinical practices (GCP) Guidelines

Dr. Umakant Bajaj Aug 11

What is clinical practice ?

The

study involving human beings.

The practice of treating patients with the use medicines/drugs.

What is good clinical practice?

Set of guidelines for biomedical research in human beings that includes

Design of a trial Conducting a trial Monitoring Audit Analysis Reporting Publishing

Good clinical practice (GCP)

Good clinical research practice (An international ethical and scientific standard for designing, conducting and reporting clinical trials that involve the participation of human subjects).

Why GCP ?

Purpose of GCP
To ensure credibility of data Consistency and authenticity of data

To protect the rights of research subjects

( Healthy volunteers or patients ) To maintain high standard of clinical research ( High quality of research )

Why GCP ?

Rights, safety & well-being of trial subjects are Protected consistent with Declaration of Helsinki and that the clinical data are credible.

Why GCP ?
Helps the sponsors/investigators

Provides sponsors and investigators a framework to conduct clinical trials according to guidelines so as to conform to high ethical and scientific standards.

Whom does the GCP apply ?

GCP is applicable to
Prophylactic, diagnostic and therapeutic trials Drugs, devices and procedures

Epidemiological studies

Who are the stakeholders/conductors for GCP ?

Sponsors Investigators Ethics committee members Regulators

When do you follow GCP ?

Planning a protocol & case record forms (CRF) Regulatory and ethical approval Trial documents Patient recruitment Monitoring Study termination Data analysis and writing report

Evolution of GCP

Research in 18th century

Edward Jenner (1749-1823) tested smallpox vaccines on his son and neighborhood children.

It is not cruel to inflict on a few, criminal sufferings which may benefit multitudes of innocent people through all centuries .Celsius

Medical experiments resulting in death

Sea water experiment High altitude experiments

Nuremberg Code 1949

10 points

Voluntary (informed) consent must be obtained by the investigator. The degree of risk should not exceed the benefit to the society. Experiment to avoid unnecessary physical or mental injury..

Tuskegee syphilis study

American medical research project conducted by the U.S. public health service from 1932 to 1972, examined the natural course of untreated syphilis in black American men.

Tuskegee syphilis study

Tuskegee study contd. Till 1997 Results

28 deaths 100 cases of disability 19 cases of congenital syphilis

Clinton had to apologize

Declaration of Helsinki, 1964

Adopted by the 18th World medical assembly. Revised 5 times Latest version 2000, Edinburgh, Scotland Two points of clarification added subsequently: 2002 (Washington) and 2004 (Tokyo).

Declaration of Helsinki, 1964

32 principles Para 13 : Protocol must be submitted to an Ethics Committee for review, which must be independent of the investigator, the sponsor,or any other kind of undue influence.

The Belmont report

Ethical principles and guidelines for the protection of Human subjects of research.
The national commission for the protection of human subjects of Biomedical and behavioral research. April 18, 1979.

Fundamental principles of Human research ethics

Respect for persons Beneficence Justice

Indian GCP guidelines

ICMR: Ethical guidelines for biomedical research, 2000 2001 Indian GCP guidelines 2005 Schedule Y of Drugs and cosmetics Act Amendment : pertinent to clinical trials

ICH GCP Guidelines

A gold standard for good clinical practices - Guidelines

ICH International Conference on Harmonization,1996

Joint initiative by regulators and industry from three regions:

US, EU, Japan

Three observers:
WHO Canada IFPMA (International Federation of

Pharmaceutical Manufacturers Association)

ICH
What is ICH ? 1. International Conference of Harmonization.

2. It is a joint initiative involving regulators & industry as equal partners in scientific & technical discussions of the testing procedures that are required to ensure and assess the safety, quality & efficacy of medicines.

ICH
The need to Harmonize Rapid increase in laws, regulations & guidelines for reporting & evaluating data on safety,quality & efficacy of new medicinal products (1960s-70s) Diff. regulatory systems with divergent technical requirements made it necessary for Industry to duplicate time-consuming & expensive test procedures for diff. markets Rising costs of healthcare, R&D costs & minimum delay in making safe & effective new treatments available to patients.

ICH
Structure Three countries, USA, Japan and EU, with their 6 founding member parties (EU, EFPIA, MHLW, JPMA, FDA and PhRMA) Observers (WHO, EFTA, Canada) - Nonvoting members. IFPMA representative

ICH operates via the ICH Steering Committee, i.e. 6 parties & IFPMA.

ICH
Parties: European Commission European Union (EU) European Federation of Pharmaceutical Industries Associations (EFPIA) Ministry of Health, Labour and Welfare, Japan (MHLW) Japan Pharmaceutical Manufacturers Association (JPMA) US Food & Drug Administration (FDA) Pharmaceutical Research & Manufacturers of America (PhRMA) International Federations of Pharmaceutical Manufacturers Association (IFPMA)

GOOD CLINICAL PRACTICE (GCP)

An international ethical and scientific quality standard for designing, conducting and reporting clinical trials that involve the participation of human subjects. Provides public assurance that rights, safety & well-being of trial subjects are protected, consistent with Declaration of Helsinki and that the clinical data are credible.

ICH-GCP
1. 2. 3.

4.
5. 6.

7.
8.

Table of Contents - 8 sections Glossary The Principles of ICH-GCP Institutional Review Board/Independent Ethics Committee (IRB/IEC) Investigator Sponsor Clinical Trial Protocol & Protocol Amendment(s) Investigators Brochure Essential Documents for Conduct of a Clinical Trial

ICH Guideline for GCP

Glossary of Imp Terms Functions & Responsibilities of
Describes Format & Content of
IRBs/IEC, sponsor, investigator

Clinical Trial Protocol Investigators Brochure

http://www.emea.eu.int/

Provides a List of Essential Documents

Principles of ICH GCP

Clinical trials to be conducted in acc with ethical principles that have their origin in the DoH & consistent with GCP & regulatory requirement(s).

Foreseeable risks & inconveniences to be weighed against the anticipated benefit for the individual trial subject & society.
The rights, safety, & well-being of the trial subjects are the most important considerations & should prevail over interests of science & society.

Principles of ICH GCP

The available non-clinical and clinical information on an investigational product should be adequate to support the proposed trial.

Clinical trials should be scientifically sound, & described in a clear, detailed protocol. A trial should be conducted in compliance with the protocol that has received prior IRB/IEC approval/favorable opinion.

Principles of ICH GCP

The medical care given to, & medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician .

Each individual involved in conducting a trial should be qualified by education, training, & experience to perform his/her resp task(s).
Freely given informed consent should be obtained from every subject prior to clinical trial participation.

Principles of ICH GCP

All trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation & verification.
Confidentiality of records that could identify subjects should be protected.

Principles of ICH GCP

Investigational products should be manufactured, handled, & stored in acc with Good Manufacturing Practice (GMP). Systems with procedures that assure quality of every aspect of trial should be implemented.

ICH-GCP
Q How does the ICH-GCP ensure ethical research? By laying down guidelines to be followed by:
IEC/IRB Investigator Sponsor

GCP INDIA(Guidelines )

GCP-INDIA
It is widely recognized that India offers unique

opportunities for conducting clinical trials, because Large patient pool Well-trained investigators Premier medical institutes Considerably low costs, per patient

-Dr.S.P. Agarwal, DGHS, New Delhi

India Ideal Destination for Clinical Trials

By 2010, global pharma majors would spend around $1-1.5 billion for drug trials in India. - McKinsey & Co India has the largest pool of patients with many diseases, including cancer and diabetes. - Rabo India Finance

India Ideal Destination for Clinical Trials

700,000 specialty hospital beds, 221 medical colleges Skilled English-speaking medical personnel. Biggest advantage is the low cost.(Rabo study) e.g. trials for a standard drug in the United States can cost about $150 million. A similar drug could be tested in India at a 60 per cent reduction of that whopping cost.

Golden Opportunity
Clinical trials in India in 2002 generated $70 million in revenues - Confederation of Indian Industry study. It predicts that it would grow to $200 million by 2007 and anywhere between $500 million and $1 billion by 2010.

GCP-INDIA
Introduction Hippocratic Oath-Do no harm to the patients GCP is an elaborate set of guidelines that address a physicians ethical & scientific responsibilities while involved in biomedical research GCP is a set of guidelines for biomedical studies involving human subjects GCP guidelines seek to establish 2 cardinal principles: a. Protection of the rights of human subjects & b. Authenticity of biomedical data

GCP-INDIA
7 topics covered in Indian GCP: 1. Definitions 2. Pre-requisites for the study 3. Responsibilities (Sponsor, Monitor, Investigator) 4. Record keeping & Data handling 5. Quality Assurance 6. Statistics 7. Special Concerns

GCP - INDIA
1.Definitions:Similar to Glossary of the ICH GCP guidelines Additional Information a. Audit of a Trial b. Phases of CTs c. Blinding / Masking d. Contract e. Escape treatment f. Non Clinical study g. Raw data h. Regulatory Authority i. Validation

GCP - INDIA
2. Pre-requisites for the study:Refers to Sch Y of Drug and Cosmetics Act. Details of Protocol Requirements Ethical & Safety Considerations Informed Consent Process Special Groups for CTs e.g. children

GCP - INDIA
3. Responsibilities:-

Sponsor Investigator Monitor

GCP - INDIA
4. Record Keeping & Data handling:Language of all written documents. Data management & query resolutions.

GCP - INDIA
5. Quality Assurance:Audits Inspections

GCP - INDIA
6. Statistics:Role of Biostatisticians Randomization & Blinding Analysis

GCP - INDIA
7.
Special Concerns:-

Vaccines Trials CT of Contraceptives CT of Medical Devices / Surgical Procedures CT with Diagnostic Agents CT with Herbal Remedies & Medicinal Plants

GCP - INDIA
Appendices:1. 2.

3.

4. 5.

DoH Schedule Y Format for Submission of Preclinical & Clinical data for r-DNA based vaccines, diagnostics & other biologicals. Investigators Brochure Essential Documents

GCP-INDIA
Formulated by an Expert Committee, set up by Central Drugs Standard Control Organization (CDSCO), with clinical experts

DTAB endorsed this GCP guidelines for clinical studies in India. Relies on ICMR Guidelines

GCP-INDIA
Ethical & Safety Considerations Principles:Essentiality Voluntariness, informed consent & community agreement Privacy & Confidentiality Precautions & Risk Minimization Professional Competence Accountability & Transparency Maximization of public interest & of distributive justice Institutional Arrangements Public Domain Totality of Responsibility Compliance

PROTOCOL

A DOCUMENT THAT DESCRIBES

The objectives Design of trial

Methodology
Organization of a trial Background and rational of trial

Source documents

Original documents, data, records and certified copies of the original records* of clinical findings,observations or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Hospital records,clinical charts, Lab notes, Evaluation checklist, Pharmacy dispensing records, x-rays, microfilm etc.

Audit

A systematic and independent examination of trial related activities and documents to determine whether the trial activities
Protocol followed
Data accurately recorded and analyzed as per

the protocol and SOPs followed and GCP followed as per the regulatory requirements

Informed consent

A process by which the subject voluntarily confirms his or her willingness to participate in the trial after having been informed of all aspects of the trial relevant to subjects decision to participate.

Investigators brochure

A compilation of the clinical and nonclinical data on the investigational product that is relevant to the study of the investigational product in human subjects.