Siriporn Pitimana-aree, M.D.,Dept. of Anesthesiology,Faculty of Medicine Siriraj Hospital

Research methodology & Ethical considerations

Research methodology & Ethical considerations

? FAQ: Frequent Ask Question ?

Why IRBs / ECs need to do a review on

research methodology ?

Scientific merit

Ethical Issues

Quality

IRB review:

Research methodology & Ethical considerations

Research Methodology

Research

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?

ResearchQuestions

ResearchObjectives

Research Question / Title

Research Question

P: Population

I: Intervention

C:

Comparison

Clinical sig.

O: Outcomes

Materials & Methods

• Target populations (Inclusion /Exclusion Withdrawal criteria)

• Sample sizeMaterials

• 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

Research Methodology & Ethical consideration

Research Title

Research objectives Scientific

Principles

Rationale

Literature review

Background

Research Methodology & Ethical consideration

Q1: What is the same consideration between research ethics and methodology?

A. Both are concern of research budget. B. Both are concern of burden of the subjects.C. Both are based on scientific principles. D. 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 ….

RiskBenefit

# 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…..

RiskBenefit

# 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.”

Research Methodology & Ethical consideration

Research subjects

Well being

Risks &

Burdens Health &

Right

Benefits

Inclusion (potential benefit)

Exclusion (possible

risk)

Withdrawal (Right, Well

being)

Risks & Benefits

Subjects

Intervention Outcomes

Design

Research Methodology & Ethical consideration

Observational study (No intervention)

• Descriptive study• Case control study• Cohort study

Research design

• Randomized control study (RCT)• Non-randomized control study • Cross - over study• Before - after study

Experimental study (Intervention)

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

Research design

Smoking is a protective factor of PONV ???

Smokers have low risk of PONV than nonsmokers

Then, you choose RCT in your study

A: No

B: Yes

Research design

Research Methodology & Ethical consideration

Q 3: What make the RCT design in smoking study unethical?

A. This design is inappropriate and will result with invalid result.B. 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.

Smokers have low risk of PONV than nonsmokers

A: Observational study B: Experimental study

What is research design?

Research design

africanpress.wordpress.com

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.

The Tuskegee Syphilis Experiment (1932-1972)

Sample Size

Sample size determination

D. I. Y. Consult Statistician

Computer program

SAMEpi-info

PS-powerN -Query

or

How large of the sample?

NOT

Too largeToo small

Unnecessary potential risks & burdens budget & resources

Unable to prove hypothesis or make conclusion

Sample size

Research Methodology & Ethical consideration

Q 4: Why too large/small samples is inappropriate in terms of research methodology and ethics?

A. Possibly let the subjects expose to unnecessary risks/burdens.

B. Inappropriate utilization of resources. C. 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

Sample size

Statistical analysis

Statistical tests should be appropriated with measurement variables design

Systematic error

Adjusted by Statistical method

Adjusted by Research method

Statistical analysis

Sample size calculation

Design

Randomization

Blinding

Chance Chance

DirectionDirection

Random error

Scientific validity

Literature review

Research Question (PICO)

Design & Sample size

Statistical tests

Ethical Principles

Research Methodology & Ethical consideration

In Summary

Research methodology & Ethical considerations

What make medical research ethical?

What make clinical research ethical?

Emmanuel EJ, Wender D, Grady C. What make Clinical Research Ethical?JAMA 2000;283: 2701-11.

1. Social & Scientific value (prophylaxis, diagnostic, therapeutic)

7 considerations:

2. Scientific sounds / principles (Methodology valid)

3. Expected research risks < Potential benefits

4. Approved by IRBs or ECs

What make clinical research ethical?

Emmanuel EJ, Wender D, Grady C. JAMA 2000;283: 2701-11.

5. Respect all research subject participants & Protect their health and rights (clear inclusion/exclusion criteria)

6. Informed consent (Comprehensive, Understandable, Voluntary)

7 considerations (cont.):

7. The refusal of a patient to participate in a study must never interfere with the patient-physician relationship.

RiskBenefit

A Heavy Price in the Name of Bad Science

Research methodology & Ethical considerations

? FAQ: Frequent Ask Question ?

Why IRBs / ECs need to do a review on

research methodology ?

Comments?

“ True success is notin the learning,

but in it’s application to the benefit of the mankind ”

“ ความสำ�าเร็จที่ �แที่�จร็�ง ม�ได้�อยู่��ที่ �การ็เร็ ยู่นร็�� แต่�อยู่��ที่ �การ็น�ามาใช้� เป็�น ป็ร็ะโยู่ช้น"แก�มน#ษยู่ช้าต่� ”