Research methodology & Ethical considerations Siriporn Pitimana-aree, M.D., Dept. of Anesthesiology, Faculty of Medicine Siriraj Hospital

FAQ: Frequent Ask Question ? Research methodology & Ethical considerations ? FAQ: Frequent Ask Question ? Why IRBs / ECs need to do a review on research methodology ?

IRB review: Research methodology & Ethical considerations Scientific merit Ethical Issues Quality IRB review:

Research Methodology Research Materials& Methods Research Objectives Question(s) Research Objectives Materials& Methods

Question & Objective What is the incidence of perioperative stroke? What are the risk / protective factors ? What are the short and long term outcomes? Does preoperative statin decrease incidence of stroke? Research Questions Research Objectives

Research Question / Title P: Population I: Intervention C: Comparison Clinical sig. O: Outcomes

Materials Methods Materials & Methods Target populations (Inclusion /Exclusion Withdrawal criteria) Sample size Materials Research design (Prospective/Retrospective; Observational/ Experimental) Research intervention(s) Outcome (s) measurement Statistical analysis Methods

# 12 : Medical research involving human subjects must conform to generally accepted “ scientific principles” be based on a thorough knowledge of the scientific literature, relevant sources of information , adequate laboratory and where appropriate, animal experimentation

Scientific Principles Research Methodology & Ethical consideration Scientific Principles Rationale Literature review Background Research Title Research objectives

& Ethical consideration Research Methodology & Ethical consideration Q1: What is the same consideration between research ethics and methodology? Both are concern of research budget. Both are concern of burden of the subjects. Both are based on scientific principles. Both are based on subject coercion & inducement.

# 9: Medical research is subject to ethical standards that promote respect for all human beings protect their health & rights Special attention is also required for those who cannot give or refuse consent for themselves “ vulnerable subjects”

# 18 : Every medical research study involving human subjects must be preceded by careful assessment of predictable risks / burden …. in comparison with foreseeable benefits …. Risk Benefit

the inherent risks & burdens to the subject….. # 21: Medical research involving human subjects should only be conducted if the importance or the potential of benefit of the objective “ outweighs” the inherent risks & burdens to the subject….. Risk Benefit

# 6: In medical research on human subjects, considerations related to “ the well-being” of the human individual subject should take precedence over all other interests.

# 32: The benefits, risks, burdens & effectiveness of a new method should be tested against those of the best current methods. “ This does not exclude the use of placebo, or no treatment, in studies where no proven method exists.”

& Ethical consideration Research Methodology & Ethical consideration Research subjects Well being Risks & Burdens Health & Right Benefits Inclusion (potential benefit) Exclusion (possible risk) Withdrawal (Right, Well being)

& Ethical consideration Research Methodology & Ethical consideration Risks & Benefits Subjects Intervention Outcomes Design

Observational study (No intervention) Descriptive study Research design Observational study (No intervention) Descriptive study Case control study Cohort study

Experimental study (Intervention) Randomized control study (RCT) Research design Experimental study (Intervention) Randomized control study (RCT) Non-randomized control study Cross - over study Before - after study

Comparison effectiveness of a new method Research design Comparison effectiveness of a new method against those of the best current methods. Q:2 What is the best research design? A. Randomized control study (RCT) B. Non-randomized control study C. Historical control D. Observational study

Smoking is a protective factor of PONV ??? Research design Smokers have low risk of PONV than nonsmokers Smoking is a protective factor of PONV ??? Then, you choose RCT in your study A: No B: Yes

& Ethical consideration Research Methodology & Ethical consideration Q 3: What make the RCT design in smoking study unethical? This design is inappropriate and will result with invalid result. Risk and well being of the subjects are the major factors. C. The RCT will result with too large sample size. D. It is not based on scientific principle.

A: Observational study B: Experimental study What is research design? Smokers have low risk of PONV than nonsmokers A: Observational study B: Experimental study What is research design?

The Tuskegee Syphilis Experiment (1932-1972) The Tuskegee Experiment : An Apology at Last “ The United States government did something that was wrong …….. deeply, profoundly, morally wrong. It was an outrage to our commitment to integrity and equality for all our citizens . . . . .. clearly racist.” President Clinton's apology for the Tuskegee Syphilis Experiment to the eight remaining survivors, May 16,1997. africanpress.wordpress.com

Sample Size

Sample size determination D. I. Y. Consult Statistician or Computer program SAM Epi-info PS-power N -Query

N O T How large of the sample? Too small Too large Sample size Unnecessary potential risks & burdens budget & resources Unable to prove hypothesis or make conclusion

& Ethical consideration Research Methodology & Ethical consideration Q 4: Why too large/small samples is inappropriate in terms of research methodology and ethics? Possibly let the subjects expose to unnecessary risks/burdens. Inappropriate utilization of resources. Probably / always end up with invalid / inconclusive result. D. All of the above.

Sample size determination: Not just formula Not just number Rationale for that formula, number Appropriateness with research design Appropriateness with outcomes

Statistical analysis Statistical tests should be appropriated with measurement variables design

Random error Systematic error Chance Chance Direction Direction Adjusted by Statistical method Adjusted by Research method Design Statistical analysis Randomization Sample size calculation Blinding

Research Question (PICO) Research Methodology & Ethical consideration Scientific validity Literature review Research Question (PICO) Design & Sample size Statistical tests Ethical Principles

In Summary What make medical research ethical? Research methodology & Ethical considerations In Summary What make medical research ethical?

7 considerations: What make clinical research ethical? 1. Social & Scientific value (prophylaxis, diagnostic, therapeutic) 2. Scientific sounds / principles (Methodology valid) 3. Expected research risks < Potential benefits 4. Approved by IRBs or ECs Emmanuel EJ, Wender D, Grady C. What make Clinical Research Ethical? JAMA 2000;283: 2701-11.

What make clinical research ethical? 7 considerations (cont.): 5. Respect all research subject participants & Protect their health and rights (clear inclusion/exclusion criteria) 6. Informed consent (Comprehensive, Understandable, Voluntary) 7. The refusal of a patient to participate in a study must never interfere with the patient-physician relationship. Risk Benefit Emmanuel EJ, Wender D, Grady C. JAMA 2000;283: 2701-11.

A Heavy Price in the Name of Bad Science

FAQ: Frequent Ask Question ? Research methodology & Ethical considerations ? FAQ: Frequent Ask Question ? Why IRBs / ECs need to do a review on research methodology ?

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