Research Ethics

1. Research Ethics ……..a gist of the basic scientific etiquettes.

2. ETHICS & RESEARCH • The word “Ethic” gives a meaning about some basic rules that should be followed before implementing something actually. Ethics has much to play in the area of scientific research as the later is a long process which takes lot of time, devotion and deals with materials where extreme caution and care must be taken. Research ethics provides guidelines for the responsible conduct of research based studies. In addition, it educates and monitors scientists conducting research to ensure a high ethical standard.

3. The atomic veterans • During and after WWII, American soldiers were forced to observe nuclear blasts within 50 miles of ground zero. • Thousands of these soldiers later died of leukemia and other rare forms of cancer. • Their families were barred from suing the federal government

4. Plutonium Study (1947) • Doctors injected plutonium into the leg of Elmer Allen, a 36-year-old African-American railroad porter. • Researchers analyzed tissue sample to determine the physiological dispersion of plutonium. • They wanted to determine the lingering levels of plutonium remaining in Allen’s body from the injection 26 years earlier.

5. Radioactive oatmeal! • More than 100 boys living in an orphanage were fed Quaker Oats with radioactive iron and calcium in the 1950's. • The diet was part of an experiment to prove that the nutrients in Quaker oatmeal travel throughout the body.

6. Cloning Fraud • 2005: South Korean researcher, Woo Suk Hwang, fabricated evidence that he had successfully cloned human embryos. • The journal Science, retracted two studies he had published.

7. Outsourcing clinical trials • The price of bringing a new drug to market is about $1 million per day • Much of that cost is devoted to human clinical trials • western drug makers are outsourcing safety and efficacy studies to developing countries, a large proportion of them to India and Russia. • There are currently some 400 clinical trials underway in India

8. Where do students learn ethical decision making? • Mentor, advisor • 2. Fellow graduate students • 3. Family • 4. Friends not in graduate school • 5. Other faculty • 6. Religious beliefs • 7. Discussions in courses, labs, seminars • 8. Professional organizations • 9. Courses dealing with ethical issues • J. P. Swazey, K. S. Louis, and M. S. Anderson, “The ethical training of graduate students requires serious and continuing attention,” Chronicle of Higher Education 9 (March 1994):B1–2; J. P. Swazey, “Ethical problems in academic research,” American Scientist 81(Nov./Dec. 1993):542–53.

9. ORIGIN & HISTORY OF RESEARCH ETHICS • The birth of research ethics took place in order to save human subject involved in research. • The first trials, called “Nuremberg Trials were done on Nazi war criminals in 1946-47 where great torture was done with the wounded , crippled men of war. • Hence, to prosecute the guilty doctors, a set of ethical guidelines were formulated which called the “Nuremberg Code” (August, 1947). This code formed the first step that spoke of ethics in human based research. • The Nuremberg Guidelines paved the way for the next major initiative designed to promote responsible research with human subjects, the “Helsinki Declaration” (June, 1964; Fourth revision: 1996) that lays out basic ethical principles for conducting biomedical research and specifies guidelines for research conducted either by a physician, in conjunction with medical care, or within a clinical setting. • Following the Helsinki Declaration, the next set of research ethics guidelines came out in the “Belmont Report” (Issued Sept., 1978; Published: April, 1979) for the protection of Human Subjects of Biomedical and Behavioral Research.

10. HELSINKI DECLARATION: The necessity of using an independent investigator to review potential research projects. Employing a medically qualified person to supervise the research and assume responsibility for the health and welfare of human subjects. The importance of preserving the accuracy of research results. Suggestions on how to obtain informed consent from research participants Rules concerning research with children and mentally incompetent persons Evaluating and using experimental treatments on patients The importance of determining which medical situations and conditions are appropriate and safe for research BELMONT REPORT: • The ethical principles for research with human subjects. • Boundaries between medical practice and research. • The concepts of respect for persons, beneficence, and justice. • Applications of these principles in informed consent (respect for persons), assessing risks and benefits (beneficence), and subject selection (justice) NUREMBERG CODE: • Research participants must voluntarily consent to research participation. • Research aims should contribute to the good of society. • Research must be based on sound theory and prior animal testing. • Research must avoid unnecessary physical and mental suffering • No research projects can go forward where serious injury and/or death are potential outcomes • The degree of risk taken with research participants cannot exceed anticipated benefits of results • Proper environment and protection for participants is necessary • Experiments can be conducted only by scientifically qualified persons • Human subjects must be allowed to discontinue their participation at any time • Scientists must be prepared to terminate the experiment if there is cause to believe that continuation will be harmful or result in injury or death.

11. Informed Consent • African-American Slaves and Medical Experimentation“…blacks were particularly easy targets, given their positions as voiceless slaves or ‘free persons of color’ in a society sensitive to and separated by race.”Todd L. Savitt (1982). “The Use of Blacks for Medical Experimentation and Demonstration in the Old South” Journal of Southern History, Vol. 48 (3):331-348.

12. Secret Human Experiments • Willowbrook Study (Early 1960s) • Willowbrook State School in Staten Island, NY conducted research on vulnerable, mentally retarded children to better understand the natural history of the highly infectious hepatitis virus. • Only parents who agreed to the research were able to enroll their children into Willowbrook.

13. Secret Human Experiments • Jewish Chronic Disease Hospital Study (1963) • Studies were conducted at what is now the Interfaith Hospital of Brooklyn • Unwitting, unsuspecting, and unconsenting patients were monitored by doctors to determine the body’s ability to reject cancer cells. • Doctors injected live cancer cells intravenously into patients and watched for signs of neoplasia (new growth). • In reaction to this study, in 1966 the FDA (Food and Drug Administration) issued clear requirements for informed consent in research.

14. Secret Human Experiments • The Cincinnati Project (1966) • The military’s aim was to determine how much radiation military personnel could endure before becoming unable to function effectively in combat. • Subjects were treated with high doses of radiation. • Amelia Jackson was treated with 100 rads of full-body radiation (equivalent to 7,500 chest X-rays) and was never able to care for herself after the treatment.

15. Research with human subjects • With research involving human subjects the risks and costs must be balanced against the potential benefits • Trivial or repetitive research is may be unethical where the subjects are at risk After years of experimentation the scientist proved that children become addicted to nicotine

16. Autonomy • The ethical principle of autonomy means that each person should be given the respect, time, and opportunity necessary to make his or her own decisions. • Prospective participants must be given the information they will need to decide to enter a study or not to participate. • There should not be pressure to participate.

17. Vulnerable participants • Potentially vulnerable participants such as children, the elderly, the mentally ill may be incapable of understanding information that would enable them to make an informed decision about study participation. • Consequently, careful consideration of their situation and needs is required, and extra care must be taken to protect them. • For example, how will you assess the diminished capacity of an elderly individual, who will be the guardian, and how and when will you involve another individual as guardian in the process?

18. The process of obtaining consent • Identify participant population • Produce information sheet and consent document • Obtain permission from school’s ethics committee • Present research information to participant and discuss its contents – indicating that withdrawal at any time is possible • Answer participants questions • Give a copy of the consent document • Allow the participant time to consider • Meet participant and discuss documents, to answer any more questions and assess participants understanding • Obtain appropriate signed consent • Start research

19. The participants • The participants may not have the experience or educational background in order to fully understand the implications of the research • They may be swayed because of their respect of and trust in the researcher who stands as an authority figure • If they are being paid for their participation they may be swayed by economic considerations from a free judgement of the risks

20. Peer pressure • The participants may be subject to social pressure of their peer group • This is particularly prevalent in research groups

21. Assessing Participant Understanding An important part of the process is for the researcher to ensure that the prospective participants understands the research, their role in it, and any risks they may be taking. During discussion the use of open-ended and nondirective questions (i.e. those that begin with words such as "what," "where," "how often," "when," and "please describe.“) is most effective at doing this .

22. Contact Information Give the names of people who can answer questions about the research; include the principal investigator. If the researcher is a student, include the names and phone numbers of the principal investigator and, where applicable, the chair of the school ethical committee for questions. Furnish the contact name of a neutral third party who can explain the rights of research participants if the participant has any questions.

23. Withdrawal • Always stress the fact that participation is voluntary and that the participant can withdraw at any time • State that refusing to participate will involve no penalty or decrease in benefits to which the participant is otherwise entitled. • Emphasize that the individual may discontinue participation at any time without penalty or loss of benefits. • If there are limitations or risks involved in withdrawal, such as a danger to the participant's well being, these must also be clearly explained.

24. Ethical problems may arise The requirements of effective research sometimes conflict with the simple fulfillment of the obligation to obtain informed consent. For example • in psychological research information and fore-knowledge may bias the results

25. Reasons for limiting information • The most common reason for limiting information is that valid data could not be obtained if the participants were fully informed about the purposes and procedures of the research. • Methodological requirements of the research may demand that the participants remain unaware of the specific hypotheses under investigation. • In other situations, incomplete information or misinformation may have to be provided to elicit the behavior of a naive individual or to create psychological reality under conditions that permit valid inference.

26. Deception or concealment Fully informed consent cannot be obtained in some kinds of research without the possibility that the results may be biased In those circumstances where a methodological requirement may necessitates the use of concealment or deception, the researcher has a special responsibility 1. to determine whether the use of such techniques is justified by the study's prospective scientific, educational, or applied value 2. whether alternative procedures are available that do not use concealment or deception 3. that the participants are provided with sufficient explanation as soon as possible. These issues should be explored before undertaking the research with colleagues, supervisor(s) and the school/departmental ethics committee.

27. Risk assessment Research is by nature uncertain. • The researcher may not be fully aware of the possible hazards involved in the proposed research. • For example in the early stages of the development of new drugs their long term effects may not be known. • In these circumstances the participant may not be fully informed of potential risks.

28. The perception of risk is central to informed consent RISK A participant in research will probably not have the experience to perceive the risk directly and may be confused by mixed messages of virtual risk and so rely on the researcher’s understanding of risk

29. Consent Form I have read the Information Sheet and have had the details of the study explained to me. My questions have been answered to my satisfaction, and I may ask further questions at any time. I understand I have the right to withdraw from the study at any time and decline to answer any particular questions. I agree to provide information to the researcher(s) on the understanding that my name will not be used without my permission. I agree/do not agree to the interview being recorded electronically. I understand that I have the right to ask for the tape to be turned off at any time during the interview I agree to participate in this study under the conditions set out in the information sheet Signature – Name - Date • Might take the following form

30. Research Publication and Ethics

31. Scientific Knowledge The object of research is to extend human knowledge beyond what is already known. But an individual’s knowledge enters the domain of science only after it is presented to others in such a fashion that they can independently judge its validity. (NAP, “On Being a Scientist” 1995)

32. Three sets of obligations of a researchers to adhere to professional standards. • An obligation to honour the trust that their colleagues place in them. • 2. An obligation to themselves. Irresponsible conduct in research can make it impossible to achieve a goal. • 3. An obligation to act in ways that serve the public. • On Being Scientist • http://www.nap.edu/catalog/12192.html • Available free for one download

33. Sharing Scientific Knowledge • “Science is a shared knowledge based on a common understanding of some aspect of the physical or social world” • Presentations • Social conventions play an important role in establishing the reliability of scientific knowledge • Publications in peer reviewed journals • Research results are privileged until they are published • Thesis • (NAP, “On Being a Scientist” 1995)

34. Why Publish? • “A paper is an organized description of hypotheses, data and conclusions, intended to instruct the reader. If your research does not generate papers, it might just as well not have been done” (G. Whitesides, Adv. Mater., 2004, 16, 1375) • “if it wasn’t published, it wasn’t done” - in (E.H. Miller 1993)

35. BASIC ISSUES IN RESEARCH ETHICS RESEARCH ETHICS The following drawing shows the basic research ethics issues. Authorship Plagiarism Peer review Conflicts of interest Research misconduct Data management Research with animals Research with human subjects

36. 1. Authorship It is the process of deciding whose names belong on a research paper. Basic guidelines: • Each person listed as an author on an article should have significantly contributed to both the research and writing. The list of authors establishes accountability as well as credit. • Policies at most scientific journals state that a person should be listed as the author of a paper only if that person made a direct and substantial intellectual contribution to the design of the research, the interpretation of the data, or the drafting of the paper. • All listed authors must be prepared to accept full responsibility for the content of the research article. • Colleagues who helped in the research indirectly must not be treated as authors rather their names should be acknowledged at the end of the paper. • All the contributing co-authors of an article must jointly decide the order of the listing of names. The first person listed should be the person most closely involved with the research.

37. Great Manuscript! But LAB CHIEF always gets listed as FIRST author! Including “honorary,” “guest,” or “gift” authors dilutes the credit due the people who actually did the work, inflates the credentials of the added authors, and makes the proper attribution of credit more difficult. (“On Being a Scientist” , NAP)

38. What is publishable…. Journals like to publish papers that are going to be widely read and useful to the readers • Papers that report “original and significant” findings that are likely to be of interest to a broad spectrum of its readers • Papers that are well organized and well written, with clear statements regarding how the findings relate to and advance the understanding/development of the subject • Papers that are concise and yet complete in their presentation of the findings

39. What is not acceptable… • Papers that are routine extensions of previous reports and that do not appreciably advance fundamental understanding or knowledge in the area • Incremental / fragmentary reports of research results • Verbose, poorly organized, papers cluttered with unnecessary or poor quality illustrations • Violations of ethical guidelines, including plagiarism of any type or degree (of others or of oneself) and questionable research practices (QRP)

40. 2. Plagiarism It is the act of passing off somebody else’s ideas, thoughts, pictures, theories, words, or stories as your own. If a researcher plagiarizes the work of others, they are bringing into question the integrity, ethics, and trustworthiness of the sum total of his or her research. Basic guidelines: A researcher preparing a written manuscript should cite the original source if he or she: • “Quotes another person’s actual words, either oral or written; • Paraphrases another person’s words, either oral or written; • Uses another person’s idea, opinion, or theory; or • Borrows facts, statistics, or other illustrative material, unless the information is common knowledge.

41. 3. Peer review It is the process in which an author (or authors) submits a written manuscript or article to a journal for publication and the journal editor distributes the article to experts working in the same, or similar, scientific discipline. Basic guidelines: • Reviewers should not know the author (or authors) they are reviewing, and the author (or authors) should not be told the names of the reviewers. • No person involved in the peer review process – either the editor, reviewers, or other journal staff – can publicly disclose the information in the article or use the information in a submitted article for personal gain. • Peer reviewers, in addition to maintaining confidentiality, can be neither conflicted nor political in their review. • Peer reviewers should disclose all conflicts of interest that may unduly influence their review to the journal editor and disqualify themselves when appropriate. • All submitting authors and readers should be fully aware of a journal’s process of peer review. • Editors must not relinquish too many of their own responsibilities to peer reviewers. • Editors should have full and complete freedom over the content of a published journal.

42. 4.Conflicts of interest Conflicts of interest arise when a person’s (or an organization’s) obligations to a particular research project conflict with their personal interests or obligations. A researcher should attempt to identify potential conflicts of interest in order to confront those issues before they have a chance to do harm or damage. Basic guidelines: According to the “Objectivity in Research NIH Guide,” an investigator should: • Disclose to their institution any major or significant financial conflicts of interest that might interfere with their ability to conduct a research project objectively. • Disclose any such financial conflicts of interest of their spouses or dependent children

43. 5. Data management Data management, in respect to research ethics, references three issues: • The ethical and truthful collection of reliable data; • the ownership and responsibility of collected data; & • retaining data and sharing access to collected data with colleagues and the public. Basic guidelines: Researchers must accurately identify answers to the following questions to resolve and address all data management issues in a timely manner: • Who is in charge of the data? • How will data be collected? • How will data be stored and what privacy and protection issues will result from the method of storage? • Who will ensure that no data were excluded from the final results and ensure accuracy of result interpretation? • How long after the project is over will data be kept?

44. 6.Research misconduct Research misconduct is defined as fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results. It is the process of identifying and reporting unethical or unsound research. Basic guidelines: • A person suspecting a scientist of research misconduct should report the incident to a research integrity officer who should immediately look into the allegation to assess if it is both: a)research misconduct; and b) within the jurisdiction of the research institution. • The person who informs the research integrity officer of suspected misconduct (the whistleblower) should be treated with “fairness and respect” by the research institution and efforts should be made to protect their job and reputation as necessary. • The person suspected of research misconduct (the respondent) should be protected and treated with “fairness and respect” by the research institution. • The research integrity officer should strive to maintain the confidentiality of both the whistleblower and the respondent. • If the misconduct issue is a criminal one the research integrity officer should report the misconduct allegations to the proper authorities or agencies.

45. Oneway ANOVA • Analysis of variance is used to test for differences among more than two populations. It can be viewed as an extension of the t-test we used for testing two population means. • The specific analysis of variance test that we will study is often referred to as the oneway ANOVA. ANOVA is an acronym for ANalysis Of VAriance. The adjective oneway means that there is a single variable that defines group membership (called a factor). Comparisons of means using more than one variable is possible with other kinds of ANOVA analysis.

46. Why Not Use Multiple T-tests • It might seem logical to use multiple t-tests if we wanted to compare a variable for more than two groups. For example, if we had three groups, we might do three t-tests: group 1 versus group 2, group 1 versus group 3, and group 2 versus group3. • However, doing three hypothesis tests to compare groups changes the probability that we are making an error (the alpha error rate). When conducting multiple tests of significance, the chance of making at least one alpha error over the series of tests is greater than the selected alpha level for each individual test. Thus, if we do multiple t-tests on the same variables with an alpha level of 0.05, the chances that we are making a mistake in applying our findings to the population is actually greater than 0.05.

47. Logic of Analysis of Variance • The logic of the analysis of variance test is the same as the logic for the test of two population means. • In both tests, we are comparing the differences among group means to a measure of dispersion for the sampling distribution. • In ANOVA, differences of group means is computed as the difference for each group mean from the mean for all subjects regardless of group. The measure of dispersion for the sampling distribution is a combination of the dispersion within each of the groups.