Pharma

Pharma

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  ETHICAL CONSIDERATION ON UTILIZINGHUMAN SUBJECTS FOR DRUG DISCOVERY PROCESS Monika U 18BCHA12
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  INTRODUCTION The new advancesin science and medicine are a cause for celebration and jubilations, but at the same time, they need careful evaluation of risks against benefits and it raises some delicate and difficult issues of ethics. These need to be dealt with extreme sensitivity of human values with utmost care, and development of ethical guidelines for the clinical research. In view of the complexity of the subject, the guidelines can neither be exhaustive nor be static. They need to be updated, consistent with the change in the realms of science and technology.
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  HISTORY The Indian Councilof Medical Research (ICMR), New Delhi had brought a document in February 1980, ‘Policy Statement of Ethical Considerations involved in Research on Human Subject’ prepared by the Ethical Committee which is being used,not only by ICMR, but also by Research Institutions, Government Agencies, Non- government Agencies. The Central Ethics Committee on Human Research (CECHR) was constituted to consider various issues related to ethical, social and legal aspects. The Committee identified the following major areas and set up sub- Committees of experts for drawing up a set of guidelines related to clinical evaluation of drugs, epidemiological research, human genetic research, transplantation research, assisted reproductive technologies and many more.
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  INSTITUTIONAL ETHICS COMMITTEE(IEC) “Institutional Ethics Committee (IEC) is an independent body constituted of medical / scientific professionals and non-medical / non-scientific members whose responsibility is to ensure the protection of the right, safety, and well-being of human subjects involved in a trial and to provide public assurance of that protection. All proposals on biomedical researches involving human subjects should be cleared by Institutional Ethics Committee (IEC), to safeguard the welfare of the rights of the subject involved.
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  The sponsor and/ or investigator should seek the opinion of Institutional Ethics Committee regarding suitability of the protocol, methods and documents to be used in recruitment of subjects and obtaining their informed consent including adequacy of the information being provided to the subjects. The Ethics Committee is entrusted not only with the initial view of the proposed research protocols prior to the initiation of the projects but also have a continuing responsibility of regular monitoring for the compliance of the ethics of the approved programme till the same are completed.
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  SALIENT FEATURES OFIEC 1. Multidisciplinary and multi - sectoral in composition 2. Independent 3. Competent
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  GENERAL STATEMENT Medical andrelated research using human beings as subjects must necessarily ensure that: 1. The PURPOSE of research should be directed towards the increase of knowledge about human condition and for the betterment of all. 2. The research is CONDUCTED in a conducive manner. The dignity, well -being, transparency and fair professional treatment should be maintained. 3. EVALUATION must be done at all stages ensuring the safety of human life.
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  GENERAL ETHICAL PRINCIPLES Allresearch involving human subjects should be conducted in accordance with three basic ethical principles, namely respect for person, beneficence and justice. The present guidelines are directed at the application of these principles to research involving human subjects. (A) RESPECT FOR PERSONS includes at least two fundamental ethical considerations, namely 1. Respect for autonomy : It includes the idea that an individual is free to choose and to act. Both rational capacity and freedom from constraint are necessary elements. “Respect for persons” includes respecting the decisions of autonomous beings.
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  2. Protection forthose with impaired or diminished autonomy It means a recognition by the commission that these people are not capable of self determination at all times and in all circumstances. (B) BENEFICENCE – includes the ethical obligation to maximize benefits and minimize harms and wrongs. (C) JUSTICE – In the ethics of research involving human subjects the principle primarily refers to distributive justice, which means equitable distribution of both burden and the benefits of participation in research
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  TWELVE BASIC PRINCIPLES (Commonto all areas of biomedical research) PRINCIPLE OF ESSENTIALITY All biomedical researches on human subjects should be absolutely essential after a due consideration of all alternatives for the advancement of knowledge and human beings . PRINCIPLE OF VOLUNTARINESS AND INFORMED CONSENT The concept of voluntariness and informed consent shall apply to the community as a whole and to each individual member who is subject of research
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  PRINCIPLE OF NON-EXPLOITATION Irrespectiveof the socio-economic status and educational levels, research subject should be fully appraised of all risks arising as a result of research. PRINCIPLE OF PRIVACY AND CONFIDENTIALITY The identity of records of human subjects of research should be kept confidential and should not be disclosed without valid scientific and legal reasons. PRINCIPLE OF PRECAUTIONS AND RISK MINIMISATION Due care and caution is taken to ensure that research subjects are put to minimum risks / no irreversible risks.
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  PRINCIPLE OF PROFESSIONALCOMPETENCE The Research is conducted at all times by the competent and qualified persons. PRINCIPLE OF ACCOUNTABILITY AND TRANSPARENCY The research is committed in a fair, honest, impartial and transparent manner and records and data are maintained for a reasonable period. PRINCIPLE OF MAXIMISATION OF PUBLIC INTEREST AND OF DISTRIBUTIVE JUSTICE The research is conducted to benefit all human kind and not just socially better off.
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  PRINCIPLE OF INSTITUTIONALARRANGEMENTS All institutional arrangements required to be made in respect of research are made in a bonafide and transparent manner and records are properly maintained and preserved. PRINCIPLE OF PUBLIC DOMAIN After due experimentation and due evaluation, results are brought into public domain through scientific and other publications under the law in force at that time.
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  PRINCIPLE OF COMPLIANCE Allpersons concerned directly and indirectly should scrupulously observe the laid down rules, guidelines, norms, directions. PRINCIPLE OF TOTALITY AND RESPONSIBILITY It is the responsibility of all directly and indirectly involved with the research to monitor, review constantly and take remedial action at all stages of research.
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  GUIDELINES FOR DRUGTRIALS The Ethical Committee while reviewing proposals on Drug Trials will ensure that following guidelines in this regard are strictly followed. ● Clinical trial of drugs is a randomized single or double blind controlled study in human subjects, designed to evaluate prospectively the safety and effectiveness of new drugs. ● The proposed drug trials should be carried out, only after approval of the Drugs Controller General of India (DCGI), as is necessary under The Schedule Y of Drugs and Cosmetics Act, 1940. ● The investigator should also get the approval of Ethical Committee of the Institution before submitting the proposal to DCGI. ● All the guiding principles should be followed irrespective of whether the drug has been developed in this country or abroad or whether clinical trials have been carried out outside India or not.
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  PHASES OF CLINICALTRIALS The first three of the following four phases require ethical clearance : Phase I (Human / Clinical Pharmacology trial) : ➢ The objective of phase 1 of clinical trial is to determine the safety of the maximum tolerated dose in healthy adults of both sexes. ➢ At least two subjects should be administered each dose to establish the safe dose range, pharmacokinetic, pharmacodynamic effect, and adverse reaction, if any, with their intensity and nature. ➢ Investigator trained in clinical pharmacology should preferably carry out these studies. ➢ The duration of time lapsing between two trails in the same volunteer should be a minimum of 3 months. ➢ The volunteers should preferably be covered under some insurance scheme.
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  Phase II (Exploratorytrial) : ➢ These are controlled studies conducted in a limited number of patients of both sexes to determine therapeutic uses, effective dose range and further evaluation of safety and pharmacokinetics. ➢ Usually, 20 –25 patients should be studied for each dose. ➢ Studies are limited to 3 – 4 centres Phase III (Confirmatory trial) : ➢ The purpose of these trials is to obtain adequate data about the efficacy and safety of drugs in a larger number of patients from both sexes at multiple centers. ➢ Only after successful completion of phase III trials, permission is granted for marketing the drug Phase IV (Post Marketing Surveillance) : ➢ It is undertaken to obtain additional information about the drug’s risks, benefits and optimal use Long term effects and adverse drug reaction if any should be brought to the notice of Ethics Committee.
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  GUIDELINES FOR VACCINETRIALS The Ethical Committee while reviewing proposals on vaccine trials will ensure that the guidelines in this regard are strictly followed. The phases of these trials differ from drug trials as given below : Phase I : This refers to the first introduction of a vaccine into a human population for determination of its safety and biological effects including immunogenicity. This phase includes study of dose and route of administration and should involve Low risk subjects. For example, immunogenicity to hepatitis B vaccine should not be determined in high risk subjects. Phase II : This refers to the initial trial examining, effectiveness (immunogenicity) in a limited number of volunteers. Vaccines can be prophylactic and therapeutic in nature. Prophylactic vaccines are given to normal subjects, therapeutic or curative vaccines may be given to patients suffering from particular disease.
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  Phase III : ➢This focuses on assessment of safety and effectiveness in the prevention of disease, involving controlled study on a larger number of volunteers (in thousands) in multi-centres. ➢ Vaccines that contain active or live – attenuated microorganisms can possibly possess a small risk of producing that particular infection. ➢ The subject to be vaccinated should be informed of the same. ➢ The subjects in control groups or when subjected to ineffective vaccines run a risk of contracting the disease. ➢ The risks associated with vaccines produced by recombinant DNA techniques are not completely known. However, for all the recombinant vaccines / products the Guidelines issued by the Department of Biotechnology should be strictly followed.