Medical Research Ethics Dr. Alaa Gouda MSc Medical Research Ethics Dr. Alaa Gouda MSc. ,FACCP, EDIC Assistant Consultant KAMC-ICU Managing Editor of Journal Annals of Thoracic Medicine

What is Research? Medical research studies are designed to provide information on health or disease. Medical research studies often aim to advance our knowledge of a medical condition. Each study tries to answer specific questions. Medical research finds new ways to treat and prevent disease.

Research is beneficial Can bring benefits, good, better lives, safer lives… No argument there. Research is a good thing.

Research entails risks No research is risk free Some risks can be anticipated Some risks can be mitigated Some risks can be avoided But because it is research we cannot anticipate all risks

Types of research Observational studies follow the same group of people over time to find out what happens to their health. Epidemiological studies look for patterns of diseases in large groups of people. Intervention studies look at ways to change behaviors that affect health. Prevention studies look for ways to keep people from getting sick. Clinical trials are performed to learn the best ways to treat or, sometimes, to prevent disease

What is Ethics ? Ethics: The discipline of dealing with what is good and bad, with moral duty and obligation A set of moral principles or values The principle of conduct governing an individual or group

Research ETHICS Research ethics concerns the responsibility of researchers to be honest and respectful to all individuals who are affected by their research studies or their reports of the studies’ results.

ETHICS in Research Valid research question Purpose ? promotion IRB Data collection Consent Methodology , randomization Writing , no plagiarism Statistics Honest conclusion Submission and Publication process Disclosure , funds No bias at any stage

Unethical Examples Breaking and re-breaking of bones ( to see how many times they could be broken before healing failed to occur) Malignant melanoma study NEJM . The Tuskegee Syphilis Study NEJM . Milgram’s obedient study Pfizer off label use of Gabapanthin 430 M $ “Stanford Prison Study” brutality among guards

The response Nuremberg code http://www.med.nus.edu.sg/phar/sgcpp/nuremburg.htm Declaration of Helsinki www.wma.net CIOMS Statement http://www.cioms.ch/ Tri-Council Policy Statement (Canada) National Committee on Ethics in Human Research (Canada) http://ncehr-cnerh.org/ Belmont Report (US) Office of Human Research Protection (US) http://ohrp.osophs.dhhs.gov/index.html MRC guidelines (http://www.mrc.ac.uk/ethics UK) British Sociological Society (UK) Nuffield Reports (UK) http://www.nuffieldbioethics.org/home/index.asp Research Ethics Boards

Nuremberg Code 1947 (10 principles) Required is the voluntary, well-informed, understanding consent of the human subject in a full legal capacity. The experiment should aim at positive results for society that cannot be procured in some other way. It should be based on previous knowledge . The experiment should be set up in a way that avoids unnecessary physical and mental suffering and injuries. It should not be conducted when there is any reason to believe that it implies a risk of death or disabling injury.

Nuremberg Code The risks of the experiment should be in proportion the expected humanitarian benefits. Preparations and facilities must be provided that adequately protect the subjects against the experiment's risks. The staff who conduct or take part in the experiment must be fully trained and scientifically qualified. The human subjects must be free to immediately quit the experiment at any point when they feel physically or mentally unable to go on. Likewise, the medical staff must stop the experiment at any point when they observe that continuation would be dangerous.

The Declaration of Helsinki World Medical Association (1964, 1975, 1983, 1989, 1996, 2002) “The well-being of the subject should take precedence over the interests of science and society” Consent should be in writing. Use caution if participant is in dependent relationship with researcher Limited use of placebo, especially if treatment is available Greater access to benefit once research is concluded Epi 227 - 4 April 2008

Council for International Organizations of Medical Science (CIOMS) Guidelines 1993, 2002 Nuremberg => Helsinki => CIOMS Informed consent Research in developing countries Protection of vulnerable populations Distribution of the burdens and benefits Role and responsibilities of ethics committees Epi 227 - 4 April 2008

The Belmont Report (The U. S The Belmont Report (The U.S. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 1978) Ethical Principles and Guidelines for the Protection of Human Subjects of Research: Respect –autonomy , Individuals should consent to participate in studies and those who cannot give their consent, such as children, people with diminished abilities, and prisoners, need to be protected. Beneficence – promote good , minimize risks, and maximize possible benefits. Non-maleficence The researcher not harm the participants. Justice – fairness in procedures for selecting participants Epi 227 - 4 April 2008

APA Guide 2000 The researcher is obligated to protect participants from physical or psychological harm. During or after a study, participants may feel increased anxiety, anger, lower self- esteem, or mild depression, especially in situations in which they feel they have been cheated, tricked, deceived, or insulted. The general concept of informed consent is that human participants should be given complete information about the research and their roles in it before agreeing to participate.

Six Norms of Scientific Research Valid research design – takes into account relevant theory, methods, and prior findings Competence of researcher – capable to carry out the procedures Identification of consequences – assessment of risks and benefits (maximizing benefit and minimizing risk) Selection of subjects – appropriate to the purposes of the study, representative of the population that will benefit from the research and appropriate in number

Six Norms of Scientific Research Voluntary informed consent – obtained before study begins, without undue threat or inducement, with enough information, and agreement to participate. Compensation for injury – responsibility for what happens to the subject .

Research in Humans

Justification of Research in Humans If you’re going to treat humans, you must study humans Impossible to reach the important conclusions without studying humans. Human physiologic studies, because animal responses often are not the same Epidemiological studies, because they depend on human susceptibilities and human interactions Agents for treating humans because animal experiments don’t always predict results. Epi 227 - 4 April 2008

Guiding principles Autonomy and respect Beneficence Non-maleficence Utility Justice Scientific validity Honesty

Respect for Participants Respect for autonomy and human dignity Informed Consent Honesty Confidentiality fairly applied Fair recruitment procedures Follow up

Informed Consent for Research Information… Who is conducting and funding the study What the study is about What are the alternatives What are the risks What are the benefits What if they want to withdraw Permission

Must be… Clear and meet the patient’s needs Honest as far as possible Obtained in advance Signed or recorded (unless waived by IRB) Voluntary, not influenced Allow time to ask questions and consider Continual or repeated

Beneficence / Non-maleficence Given that we will ask persons to take risks for the benefit of others we must do what we can do mitigate these risks and avoid them wherever possible Duty to do good Duty to do good research Duty to anticipate and avoid harm Balance Benefit and Risk

Assure That Benefits Outweigh Risks Benefits must outweigh risks. Researchers must protect participants from harm and maximize their well-being. Risks or harms and benefits may be physical (pain or injury), psychological, social, economic, or legal. Risks or benefits of research may apply to individual participants, families, groups or organizations, communities, or nations. Epi 227 - 4 April 2008

Utility Make best use of scarce resources Research participants are a valuable resource Ensure value of the research question Ensure quality of method

Justice & Inclusiveness Given that risks cannot be avoided altogether But are justified because of the benefits research confers Justice asks us to share the burdens and benefits of research fairly Fair distribution of risks Do not over burden participants Fair distribution of benefits Give everyone access to the benefits of being studied and of study outcomes

Now you decided to do a Research……

Clinical Equilibrium This means that a researcher can compare treatments when: a. there is honest uncertainty about which treatment is best. b. there is honest professional disagreement among experts concerning which treatment is best.

Explain why and ensure understanding Researchers often tell participants exactly what will be done in the study but usually do not explain why. Simply telling participants about the research does not necessarily mean they are informed, especially in situations in which the participants may not be competent enough to understand. Voluntary Participation: Participants may feel forced to participate or perceive that they have limited choice.

Deception Passive deception ( or omission) is the withholding or omitting of information; the researcher intentionally does not tell participants some information about the study. Active deception ( or commission) is the presenting of misinformation about the study to participants. The most common form of active deception is misleading participants about the specific purpose of the study.

Example 1. Asch (1952, 1965) To assure participant’s participation , they hide the side effect of a drug intentionally. Example 2. Heine & Kitayama (2000) To observe participants’ natural motivation toward a task, they videotaped the participants’ behavior using hidden camera. Example 3. Masuda & Nisbett (unpublished) They eliminate the title of the research which would have indicated that it concerns differences between Japan and the US. As a result the participants were unaware that their responses would be compared with those made by individuals in the other culture

Justified Deception The deception must be justified in terms of some significant benefit that outweighs the risk to the participants. The researcher must consider all alternatives to deception and must justify the rejection of any alternative procedures. E.g. Minor side effect of the drug for the significant benefits of the drug. (HIV example)

Debriefing / Confidentiality The final point is that deceived participants must receive a debriefing that provides a full description of the true purpose of the study, including the use and purpose of deception, after the study is completed. The APA ethical guidelines require that researchers ensure the confidentiality of their research participants. Ensuring that participants’ records are kept anonymous. (how long you may keep the records ? )

The Institutional Review Board (IRB) Each institution is required to establish IRB The IRB is your friend Element of peer review Protects participants Protects researchers ( Ethanol proposal )

During Conducting the research……..

To ensure accuracy of scientific knowledge Fair subject selection State clear research methodology Should not falsify/modify/omit/fabricate data (Fraud) Use actual data for analysis/cannot include someone else's data Report errors Be aware of conflict of interest Should not withhold and/or ‘vaguing up’ information Data and material should be available to others

Do not present/publish paper from incomplete research or from anticipated outcomes Should not duplicate publications and submissions Should be reviewed Independently by unaffiliated individuals Citation and authorship Whenever somebody else’s work is quoted , reference should be made to the original author . Acknowledgement should include the names of person who helped

After you complete your research……….

Reporting of Research Researchers do not fabricate data. (They do not make false, deceptive, or fraudulent statements concerning their publications or research findings.) If they discover significant errors in their published data, they take reasonable steps to correct such errors in a correction, re-traction, erratum, or other appropriate publication means. They do not present portions of another’s work or data as their own, even if the other work or data source is cited occasionally.

Fraud It is important to distinguish between error and fraud. Fraud, is an explicit effort to falsify or misrepresent data. A safeguard against fraud is peer review, which takes place when a researcher submits a research article for publication. Replication is repetition of a research study using the same basic procedures used in the original to test the accuracy.

Plagiarism You can literally copy an entire paper word for word and present it as your own work or you can copy and paste passages from articles and sites found on the Internet.

Remember Do not include names without participation in the research Do not submit to many journals No copy / paste Do not manipulate data Do not start before IRB approval Conflict of interest/disclosure Informed consent Do not steal other’s work/ideas

Why should there be research ethics? To protect participants /patients /society /resources /researcher? To ensure accuracy of scientific knowledge To protect intellectual and property rights

Thank You