Ethics in Drug Discovery

28/02/2024 Ethics in Drug Discovery Dr Z.Elsaid Z.Elsaid@wlv.ac.uk Learning outcomes By the end of this session, and with additional reading, you should be able to: • Recall the various guidelines and legislations related to human and animal testing • Understand the history involving human experimentation which lead to ethical guidelines • Understand the importance of data publication • Describe the principles of ethics involved in human trials and animal procedures 1 28/02/2024 What is Ethics? • Derived from the Greek word ethos which can mean custom, habit, character or disposition • Concerned with what is good for individuals and society and is also described as moral philosophy • System of moral principles • Affect how people make decisions and lead their lives • Ethics covers the following dilemmas… • • • • how to live a good life our rights and responsibilities the language of right and wrong moral decisions - what is good and bad? • Our concepts of ethics have been derived from religions, philosophies and cultures • Today we are going to concentrate on ethics in clinical research on humans and animals Importance of ethics https://www.cdc.gov/tuskegee/timeline.htm 2 28/02/2024 Importance of ethics “Berta was a female patient in the psychiatric hospital. Her age and the illness that brought her to the hospital are unknown. In February 1948, Berta was injected in her left arm with syphilis. A month later, she developed scabies (an itchy skin infection caused by a mite). Several weeks later, [lead investigator Dr. John] Cutler noted that she had also developed red bumps where he had injected her arm, lesions on her arms and legs, and her skin was beginning to waste away from her body. Berta was not treated for syphilis until three months after her injection. Soon after, on August 23, Dr. Cutler wrote that Berta appeared as if she was going to die, but he did not specify why. That same day he put gonorrheal pus from another male subject into both of Berta’s eyes, as well as in her urethra and rectum. He also re-infected her with syphilis. Several days later, Berta’s eyes were filled with pus from the gonorrhea, and she was bleeding from her urethra. On August 27, Berta died.” https://bioethicsarchive.georgetown.edu/pcsbi/sites/default/files/Ethically%20Im possible%20(with%20linked%20historical%20documents)%202.7.13.pdf Importance of ethics Atrocities of human experimentation across Nazi camps in Germany. 3 types of experimentation. https://encyclopedia.ushmm.org/content/en/gallery/nazi-medical-experiments-photographs 3 28/02/2024 Nuremberg Code Nuremberg Trials = Post-war Doctors Trials in the aftermath of the Nazi experiments involving concentration camp inmates The Nuremberg Code (1947) is a set of research ethics principles for human experimentation set as a result of the subsequent Nuremberg Trials at the end of the Second World War. The declarations were reaffirmed by the World Medical Association in the Declaration of Helsinki in 1964 The Seven Major Principles • Following Nuremberg Code (1947), Declaration of Helsinki (1964 and subsequent reviews), Belmont Report (1979), CIOMS (2002) and U.S. Common Rule (1991) • Social and clinical value • Scientific validity • Fair subject selection • Favourable risk-benefit ratio • Independent review • Informed consent • Respect for potential and enrolled participants http://clinicalcenter.nih.gov/recruit/ethics.html#1 4 28/02/2024 Publishing Results • Despite being required by law, a large proportion of trial results are not published: • AllTrials.net campaign (20th January 2015) • Only 53% of clinical trials are published in journal articles • Trials with positive findings were three times more likely to be published than those with negative results • Research funded by governments was twice as likely to be published as research funded by industry • The review did not look at how many trials had reported results via clinical trial registers rather than in journal articles • Previously it has been shown results posted on trial registers contain more complete information than journal articles • Only 22 % of trials report their results promptly on a register in this way, even when required to do so by law Publishing Results Why do you think its important to publish clinical trial data? 5 28/02/2024 Publishing Results Why do you think some clinical trial data is not published? Animal Research • In Great Britain in 2019, 3.40 million procedures were carried out involving living animals. • Looking at how the body works (cause of diseases/disease progression) or assessment of treatments (safety and efficacy) or genetically-modified offspring • What do you think happens to animals? 6 28/02/2024 Animal Research • Regulation • There have been special controls on the use of laboratory animals in the UK since 1876 • These were revised and extended in 1986 with the Animals (Scientific Procedures) Act (ASPA) • ASPA has recently been revised to transpose European Directive 2010/63/EU on the protection of animals used for scientific purposes • The revised legislation came into force on 1 January 2013. This law safeguards laboratory animal welfare while allowing important medical research to continue. Animal Research https://nc3rs.org.uk/how-many-animals-are-usedresearch#:~:text=In%20Great%20Britain%20in%202019,and%20monkeys%2C%20are%20also%20used. 7 28/02/2024 UK Legislation • These controls are widely regarded as some of the strictest in the world • The act only permits research to be undertaken when all three of the below licenses have been granted • Research can only take place in research institutes or companies which have appropriate animal accommodation and veterinary facilities, and have been granted a certificate of designation • Research can only be part of an approved research or testing programme which has been given a project licence • Research can only be carried out by people with sufficient training, skills and experience as shown in their personal licence Inspections are made to ensure these are in place The Three Rs- “Replace, Reduce, Refine” • Replace the use of animals with alternative techniques, or avoid the use of animals altogether. • Could you think of alternatives? 8 28/02/2024 The Three Rs- “Replace, Reduce, Refine” • Reduce the number of animals used to a minimum, to obtain information from fewer animals or more information from the same number of animals. • Refine the way experiments are carried out, to make sure animals suffer as little as possible. This includes better housing and improvements to procedures which minimise pain and suffering and/or improve animal welfare. 9