{"id":891,"date":"2020-02-18T10:56:00","date_gmt":"2020-02-18T05:26:00","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=891"},"modified":"2020-02-18T10:56:00","modified_gmt":"2020-02-18T05:26:00","slug":"ethical-aspects-in-clinical-research","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/ethical-aspects-in-clinical-research\/","title":{"rendered":"Ethical Aspects in Clinical Research"},"content":{"rendered":"\n<p><strong>Ethical Aspects in Clinical Research<\/strong><\/p>\n\n\n\n<p><strong>Hippocratic oath<\/strong><\/p>\n\n\n\n<p>Emphasis on ethics related to \u201cmedical practice\u201d and NOT \u201cresearch ethics\u201d<\/p>\n\n\n\n<p><strong>Historical Events that have Influenced Human Research<\/strong><\/p>\n\n\n\n<p>First human subject research experiments:<\/p>\n\n\n\n<p>Vaccination trials in the 1700&#8217;s.<\/p>\n\n\n\n<p><strong>Edward Jenner<\/strong> (1749-1823) : Smallpox vaccines on his son and neighborhood children.<\/p>\n\n\n\n<p><strong>Johann Jorg<\/strong> (1779-1856) swallowed 17 drugs in various doses to record their properties.<\/p>\n\n\n\n<p><strong>Loius Pasteur<\/strong> : Rabies vaccine in a child whose death was otherwise inevitable<\/p>\n\n\n\n<ul><li><strong><em>Nazi Medical War Crimes &#8211; <\/em><\/strong>Harmful research on World war II prisoners<\/li><\/ul>\n\n\n\n<p>Led to development of:<strong> <u>Nuremberg code in 1949<\/u><\/strong><\/p>\n\n\n\n<p><strong><u>&nbsp;First set of code of International Ethics : 10 points<\/u><\/strong><\/p>\n\n\n\n<ul><li>Informed consent is essential.<\/li><li>Research should be based on prior animal work.<\/li><li>Risks should be justified by the anticipated benefits.<\/li><li>Only qualified scientists must conduct research.<\/li><li>Physical and mental suffering must be avoided.<\/li><li>Freedom to withdraw<\/li><\/ul>\n\n\n\n<p>Late 1950s : Thalidomide tragedy<\/p>\n\n\n\n<p><strong>Declaration of Helsinki June 1964, Helsinki, Finland<\/strong><\/p>\n\n\n\n<ul><li>Important in history of research ethics as the first effort of medical community to regulate itself<\/li><li>Need for Independent Ethics committees recommended<\/li><li>Modified and updated from time to time<\/li><li>11 paragraphs \u2013 37 paragraphs<\/li><li>2013 : Post-trial access, Compensation for research injury<\/li><\/ul>\n\n\n\n<p><strong>The Willowbrook Study\u00a0 (1956-71)<\/strong><\/p>\n\n\n\n<p><strong>Mentally defective children were intentionally given a mild form of a hepatitis virus<\/strong> in an attempt to study whether&nbsp; this could be an effective strategy to confer long lasting immunity after administration of gammaglobulin.<\/p>\n\n\n\n<p><strong>The Jewish Chronic Disease Hospital Study (1963)<\/strong><\/p>\n\n\n\n<p>Studies were conducted at the Jewish Chronic Disease Hospital in New York City to develop information on the <strong>nature of the human transplant rejection process. Chronically ill patients who did not have cancer were injected with live human cancer cells.<\/strong><\/p>\n\n\n\n<p>The physicians did not inform the patients as to what they were doing. The physicians\u2019 rationalization for their actions was as follows:<\/p>\n\n\n\n<p>(i) they did not want to scare the patients and (ii) they thought the cells would be rejected.<\/p>\n\n\n\n<p><strong>The Tuskegee Syphilis Study &nbsp;(1932- 1971)<\/strong><\/p>\n\n\n\n<p>&nbsp;&nbsp; Study conducted by&nbsp; U.S. Public Health Service<\/p>\n\n\n\n<ul><li>To document the natural progression of&nbsp; syphilis<\/li><li>600 low-income African-American&nbsp; males<\/li><li>Participants were not informed about their disease<\/li><li>Penicillin not administered even after availability<\/li><\/ul>\n\n\n\n<p><strong>The Belmont Report 1979<\/strong><\/p>\n\n\n\n<p>The Belmont report identified and discussed the distinction between research and practice, a discussion of the three basic ethical principles, and remarks about the application of these principles.<\/p>\n\n\n\n<p><strong>3&nbsp; fundamental ethical principles<\/strong><\/p>\n\n\n\n<ol type=\"1\"><li>Respect for persons\/ Non-maleficence -first do no harm<\/li><\/ol>\n\n\n\n<p>Incorporates two ethical convictions<\/p>\n\n\n\n<ol type=\"1\"><li>Treat individuals as autonomous human beings<\/li><li>Protect persons with diminished autonomy<\/li><\/ol>\n\n\n\n<p><strong>Application<\/strong><\/p>\n\n\n\n<ol type=\"1\"><li>Conduct initial and continuing informed consent\u00a0<\/li><li>Allow the participant to withdraw from the research<\/li><\/ol>\n\n\n\n<ol type=\"1\" start=\"2\"><li>Beneficence<\/li><\/ol>\n\n\n\n<p>2 complementary expressions of beneficent actions<\/p>\n\n\n\n<ol type=\"1\" start=\"2\"><li>Do not harm<\/li><li>Maximize possible benefits and minimize possible harms.<\/li><\/ol>\n\n\n\n<p><strong>Application<\/strong><\/p>\n\n\n\n<ol type=\"1\" start=\"2\"><li>Determine whether the research has a favourable risk-benefit ratio<\/li><li>Ensure that the research is scientifically valid<\/li><\/ol>\n\n\n\n<ol type=\"1\" start=\"3\"><li>Justice<\/li><\/ol>\n\n\n\n<p>The requirement to<\/p>\n\n\n\n<ul><li>select subjects equitably<\/li><li>avoid exploitation of vulnerable populations<\/li><\/ul>\n\n\n\n<p>Application<\/p>\n\n\n\n<ul><li>Determine whether there is a fair subject selection<\/li><li>Evaluate the inclusion and exclusion criteria and the methods of recruitment<\/li><\/ul>\n\n\n\n<p>Basic ethical principles that underlie all human subject research<\/p>\n\n\n\n<ul><li>Other international guidelines &#8211;<strong>C<\/strong>ouncil for International Organizations of Medical Sciences (CIOMS) guidelines 1982,1993,2002<\/li><li>ICH GCP guidelines, 1996<ul><li>GCP is an international ethical and scientific quality standard for designing, conducting, recording and reporting clinical trials<\/li><\/ul><ul><li>Compliance with these guidelines provides public assurance that the rights safety and well-being of trial subjects are maintained&nbsp; and that the clinical trial data are credible.<\/li><\/ul><ul><li>The objective of ICH GCP is to provide a unified standard for EU, Japan and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities under these jurisdictions<\/li><\/ul><\/li><\/ul>\n\n\n\n<p>National guidelines- &nbsp;<\/p>\n\n\n\n<ul><li>ICMR \u2013 Ethical guidelines for biomedical research on human subjects, 2006 and 2017 \u2013 general principle\u00e0<ul><li>Essentiality<\/li><li>Voluntariness, informed consent<\/li><li>Non-exploitation<\/li><li>Privacy and confidentiality<\/li><li>Precaution and risk minimisation<\/li><li>Professional competence<\/li><li>Accountability and transparency<\/li><li>Institutional arrangements<\/li><li>Public domain<\/li><\/ul><\/li><\/ul>\n\n\n\n<ul><li>Roles and responsibilities of &#8211;&nbsp;&nbsp;&nbsp; Institutional Ethics Committees<\/li><li>Ethical Issues &#8211; Informed consent process, confidentiality, compensation, vulnerable groups<\/li><li>Specific principles pertaining to vaccines trial, medical devices, diagnostics, herbal products, genetics, transplantation research<\/li><\/ul>\n\n\n\n<ul><li>Indian GCP Guidelines, CDSCO, New Delhi&nbsp; 2001<\/li><li>Revised Schedule Y: January 2013<ul><li>Reporting of SAEs occurring during clinical trials and payment of compensation in case of trial related injury or death<\/li><li>Inspection of clinical trial sites by inspectors authorized by CDSCO<\/li><li>Mandatory registration of the Ethics Committees<\/li><\/ul><\/li><\/ul>\n\n\n\n<p><strong>Ensuring ethics in research<\/strong><\/p>\n\n\n\n<ol type=\"1\"><li>Submit it to your Institutional&nbsp; Ethics Committee (IEC)&nbsp; for review<\/li><\/ol>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp; By safeguarding the dignity, rights, safety, and well-being of research participants<\/p>\n\n\n\n<p>&nbsp; <strong>Documents to be submitted to IEC for review<\/strong><strong><\/strong><\/p>\n\n\n\n<ol type=\"1\"><li>Project submission application form<\/li><li>Summary of protocol<\/li><li>Protocol<\/li><li>Informed consent document in English and Regional languages<\/li><\/ol>\n\n\n\n<ol type=\"1\" start=\"6\"><li>Case Record Form<\/li><li>Patient instruction card, identity card, diary, etc.<\/li><li>Questionnaire\/s<\/li><li>Investigator Brochure<\/li><li>Insurance policy<\/li><li>Investigator\u2019s undertaking to DCG(I)<\/li><li>Clinical Trial Agreement<\/li><li>Signed and dated brief current CV of the study team members<\/li><\/ol>\n\n\n\n<ol type=\"1\" start=\"14\"><li>Subject recruitment procedures: advertisement, notices<\/li><li>Compensation for participation<\/li><li>Compensation for research related injury<\/li><li>Regulatory approvals<ol><li>DCGI<\/li><\/ol><ol><li>HMSC approval for foreign collaborative studies<\/li><\/ol><ol><li>BARC for radioisotope studies<\/li><\/ol><ol><li>Admin approval of collaborating institutes<\/li><\/ol><\/li><\/ol>\n\n\n\n<ol type=\"1\" start=\"18\"><li>Log of delegation of responsibility of the study team members<\/li><li>Current Status of Ongoing Studies conducted by PI<\/li><li>Documentation of CTRI registration\/ any other WHO platform registry (whenever applicable)<\/li><li>GCP training certificates of PI and Co-I<\/li><\/ol>\n\n\n\n<p><strong>Elements of Review<\/strong><\/p>\n\n\n\n<ol type=\"1\"><li>Scientific Design and Conduct of the Study<\/li><li>Risk-benefit Assessment<\/li><li>Recruitment of Research Participants<\/li><li>Care and Protection of Research Participants<\/li><li>Protection of Research Participant Confidentiality<\/li><li>Informed Consent Process<\/li><\/ol>\n\n\n\n<p><strong>Role of Investigator<\/strong><\/p>\n\n\n\n<p>Requirements of Investigator-<\/p>\n\n\n\n<ul><li>Medically qualified, Competent<\/li><li>Experienced<\/li><li>Trained in GCP<\/li><li>Responsible<\/li><li>Infrastructure &#8211; Adequate number of patients, qualified staff , facilities<\/li><li>Time to conduct study<\/li><li>Integrity<\/li><\/ul>\n\n\n\n<p><strong>&nbsp;Responsibility<\/strong><\/p>\n\n\n\n<ul><li>Scientific aspects<\/li><li>Communication with IEC<\/li><li>Patient enrolment<\/li><li>Investigational product<\/li><li>Medical care of trial subjects<\/li><li>Reporting to sponsor<\/li><li>Record keeping<\/li><li>Documents&nbsp; (Preparation &amp; Submission) Protocol amendments<\/li><li>SAEs, Protocol deviations\/violations<\/li><li>Undertake informed consent process (or supervise this, if delegated)<\/li><li>Ensure staff qualifications and training<\/li><\/ul>\n\n\n\n<p><strong>Informed consent -Essential Information to be given<\/strong><\/p>\n\n\n\n<ul><li>Statement that the study involves research<\/li><li>Purpose of the research<\/li><li>Approximate number of subjects<\/li><li>Duration of the subject participation<\/li><li>Description of procedures to be followed<\/li><li>Aspects that are experimental<\/li><li>Subject\u2019s responsibilities<\/li><li>Treatment options and probability for random assignment<\/li><li>Benefits expected from research to the subject or others<\/li><li>Risks or discomforts expected<\/li><li>Need to take measures to prevent pregnancy<\/li><li>Alternative procedures or courses of treatment available<\/li><li>Freedom to participate and to withdraw from research<\/li><li>Payment for participation<\/li><li>Treatment &amp; compensation for research related injury<\/li><li>Maintenance of confidentiality of records<\/li><li>Identity of the research teams and contact persons<\/li><li>Whom to contact for rights of subjects<\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Ethical Aspects in Clinical Research Hippocratic oath Emphasis on ethics related to \u201cmedical practice\u201d and NOT \u201cresearch ethics\u201d Historical Events that have Influenced Human Research First human subject research experiments: Vaccination trials in the 1700&#8217;s. Edward Jenner (1749-1823) : Smallpox vaccines on his son and neighborhood children. Johann Jorg (1779-1856) swallowed 17 drugs in various[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/891"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=891"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/891\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=891"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=891"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=891"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}