The ethics of research

Anjum John 6/28/2009 1 1. 2. 3. 4. To discuss what the basic ethical principles of research are To evaluate some researches based on these ethical principles To study the ethical aspects of the various relationships that a researcher might acquire To find out how these ethical principles apply to research conducted in HMC 6/28/2009 2 A systematic investigation undertaken to contribute to generalizable knowledge 6/28/2009 3 A balance between :  Science to enhance the health of society Rights and welfare of individual research subjects. 6/28/2009 Welfare Rights Science/society  4 The science of developing rules of practice in respect to a single class of human actions. 6/28/2009 5 The rules of practice by which the researcher  RESEARCH ETHICS should behave towards those who participate in research.  should behave towards society in general 6/28/2009 6 Researcher Exploitation Individual participants Participants in society Generalizable knowledge Exploitation 6/28/2009 7  National Commission Conference at Smithsonian Institution’s Belmont Conference Center in Maryland  Respect for persons (human dignity) Beneficence (do good) Justice. BELMONT REPORT - April 18, April 18, 1979 6/28/2009   3 Principles that should guide ethical research 8 6/28/2009 9  Smallpox vaccination trial on his neighborhood children and his own son.  In pre-modern research, physicians used themselves or their family members as test subjects. Edward Jenner 6/28/2009 Ethical issues ? 10 Elements: 1. Do no harm 2. Maximize benefits 3. Minimize harms Applications to research  Weigh the risks  Weigh the benefits  Benefits > Risks 6/28/2009 11 Dr. Arthur Wentworth(1896) performed spinal taps on 29 hospitalized “normal” children in Boston to determine if the procedure was harmful. His aim was to see if one should wait till a patient became morbidly sick to do a spinal tap. His aim was to do a controlled experiment. 6/28/2009 12  Use of hospitalized patients- vulnerable populations  Doing spinal taps on them without explaining plan to mothers- lack of full disclosure  Giving science precedence over the individual participant ( risk Vs benefit)  IRB approval ?  Fine line between clinical practice and research 6/28/2009 13  Low pressure Experiments: Prisoners were put into lowpressure tanks to see how long they could survive with little oxygen. Many of those who did not die immediately were put under water until they died and autopsies followed.  Hypothermia Experiments: Prisoners were submerged in tanks filled with cold water. Typhus experiments: Individuals were injected with anti typhus vaccine & then infected with typhus; Individuals in the control group received no vaccine. Malaria experiments Prisoners were infected with mosquitoes carrying malaria and then given a variety of anti-malarial drugs.   6/28/2009 14 The goal of these experiments was to check how long German pilots, who had to parachute into the cold North Sea, would survive or to see how German pilots ejected from their planes would do or find out how to prevent typhus/malaria in their camps. Ethical issues      Prisoners- vulnerable populations Using healthy subjects without their consent – principle of human dignity Science > individual Risks to individual participants> Benefits to German air pilots Worth of human life ?? 6/28/2009 15 Elements: 1. Equitable selection of subjects 2. Equitable bearing of the burdens of research 3. Protection of the confidentiality of participants Applications to research 1. Equity 2. Equipoise 3. Availability of research findings to the research participants 6/28/2009 16  US Public health service initiated study to follow the natural history of untreated syphilis.  400 African American men were enrolled in the study and followed up for around 40 years. 6/28/2009 17 Deception- lack of complete disclosure  2. Withholding available and effective treatment (principle of justice)  3. Recruiting African American men : Principle of justice  4. Risks to participants and their families  5. Using a group for the benefit of others  1. 6/28/2009 18 Researches in developing countries: Council for the International Organization of Medical Sciences (CIOMS) guidelines last modified 2002 available at :http://www.cioms.ch/frame_guidelines_nov_2002.htm 2. Research in Islamic countries: ( Islamic Organization of Medical Sciences): available at : 1. http://www.islamset.com/ioms/Code2004/Islamic_visio n1.html 6/28/2009 19 A clinical trial to develop an affordable and effective treatment for HIV positive women to prevent mother to child perinatal transmission.  Conducted by investigators from 11 nations, UNAIDS,WHO,CDC, NIH  Conducted in Sub Saharan Africa, Thailand  Comparison trial of a short , less intensive AZT regimen to a placebo control  Ethical issues ? 6/28/2009 20 Furthering science All these varying interests can cause conflict of interest. Career interests Promotions Welfare of Participants Researcher interest Publications For the sake of society Fame Therefore a 3rd party impartial opinion is to be taken . = Institutional Review Board/ Research Committee 6/28/2009 21 Jesse was enrolled in a dose escalation gene transfer clinical trial at the University of Pennsylvania. He received an injection of adenovirus transfected with the ornithine transcarbamylase gene. He died later from a reaction to a gene transfer recombinant viral vector . The PI for this study was the inventor of the technology used in the trial and held equity in the company to which the technology was licensed. 6/28/2009 22  Conflict of interest  Issue of coercion because of personal interest  Incomplete disclosure 6/28/2009 23 4. Community partnership: research responsive to health needs of the community  In planning, conducting and overseeing the research.  Integrate results into the health systems of the community.  Research without social value exposes participants to unnecessary risks without a compensating societal benefit and wastes time and resources. 6/28/2009 24 5. Scientific validity: appropriate methodology to ensure that the results will answer original research questions. 6/28/2009 25 6. Fair subject selection: Avoid exploitation of vulnerable subjects  Avoid choosing groups solely on easy availability or compromised position.  Do not involve groups unlikely to benefit from the subsequent applications of the research.  Ensure that the benefits and risks of research are distributed fairly among all groups in society 6/28/2009 27 8. Favorable risk/benefit ratio:  Minimize potential risks - sound research design  Enhance potential benefits  Compare A risks and benefits favorable risk/benefit ratio embodies the principles of non-maleficence and beneficence. 6/28/2009 28 9. Informed consent : Participants should be given the opportunity to decide  whether to enroll in research and  whether research fits with their own values, interests, and goals. Respecting persons and their autonomous decisions embodies the principle of respect for human dignity. 6/28/2009 29 1. 2. Proxy decision maker An independent person/persons to Monitor the consent process Monitor the subject’s involvement in the study Ensure that the enrollment of such individuals is necessary for the conduct of the research    Protecting the rights and welfare of vulnerable populations is in keeping with the principle of respect for human dignity. 6/28/2009 30 10. Respect for enrolled participants:  Protect confidentiality of their private information Permit withdrawal at anytime and for any reason during the study Provide new information during the study if such information might affect their decision to continue in the study Monitor subjects’ welfare throughout the study 6/28/2009    31  Researcher  Researcher – RC relationship – participant relationship  Researcher – colleague/ collaborator relationship  Researcher journal editor relationship 6/28/2009 32  Should be one of openness, honesty and integrity.  Treat RC as a friend , guide and protector  Always seek RC approval for all your human subjects research 6/28/2009 33 Participant anonymity  Do not :expose   Do not :involve participants in research without their knowledge participant to mental stress :Use deception :Use coercion :Deprive participants right to self determination 6/28/2009 detrimental to participants self interests : ask questions 34  Honesty  Acknowledgements  Protection  Authorship  Conflict to participation of data safety issues of interest issues  Intellectual property issues 6/28/2009 35  Honesty  Conflict of interest declaration  Due  Not acknowledgement and credits party to scientific fraud, plagiarism etc.., 6/28/2009 36  IRB approval research proposal of head/chairman of department  Complete  Signature  Decide on investigator roles & authorship before hand  Do background search if your research has been done before 6/28/2009  Check 37  Investigator’s assurance/ no conflict of interest  Following rules and regulations of research  Contacting Staff of the Medical Research Center for any assistance  Progress reports  Compliance with protocol  Protection of participant rights and safety 6/28/2009 38  Informing  Publishing about project completion or communicating results of research  Signed informed consent 6/28/2009 39  An uninterested third party review of the proposal is done  Project approved if found suitable based on all the ethical requirements given above. 6/28/2009 40  1. Why are research ethics necessary ?  2. What are the basic principles of research ethics ?  3. What are the major events in human research that have violated ethical principles ?  4. What are the requirements to conduct ethical research ?  5. How to use the principles of research ethics to achieve a balance between the goals of human subject research  6. Role of Research Committees 6/28/2009 41 6/28/2009 42 6/28/2009 43  Woo- Suk Hwang published a paper on “ Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst”.. Around 50 researchers were credited in this paper.  This was the first time that anyone had offered proof of a cloned human blastocyst or even extracted stem cells from it, using the technique of Somatic Cell Nuclear Transfer . 1.Hwang W-S, Ryu YJ, Park JH, et al. Science 2004;303:166974;2004 2. W.S Hwang et al. Science 308,1777-1783;2005 44 6/28/2009  Eggs were collected from junior research assistants from Hwang’s lab.  Somatic cells were collected from those with congenital hypogammaglobulinemia, juvenile diabetes and spinal cord injury.  Science withdrew both papers in 2006 on charges of alleged scientific misconduct 6/28/2009 45 1. 2. 3. Payment to egg donors( coercion) Claims of cell lines derived via SCNT were fabricated Authorship for authors unrelated to the research 6/28/2009 46  Some of the somatic cell donors had spinal cord injury ( indication ??) 6/28/2009 47