Structure of Research Proposal

• Set of ethical principles regarding human experimentation
• Provides for a higher standard of human protection
• Last revision – 2013

• Basic principles:

–respect for the individuals and their rights, including the right to make informed decision

–subject's welfare must always take precedence over the interests of science and society

–ethical considerations must always take precedence over laws and regulations

PICO (TS) method:

• Patient or population at hand
• Intervention or Exposure
• Comparison
• Clinical Outcomes
• Additional elements: Time, Setting (eg, primary care, specialty, inpatients etc.)

• Permission before a healthcare intervention
• Always required in research
• Valid informed consent is based upon:

–Disclosure: discussion of pertinent information

–Understanding: ability to comprehend

–Capacity: ability to make decisions

–Voluntariness: freedom from coercion/manipulation

• Surrogate consent considered when

–Research participant is incompetent

–Physically or mentally incapable of giving consent

–Participant is a minor

• Surrogate should act in the subject's best interest

Additional guidelines and regulations

• Good clinical practice (GCP)

–International guide

–Quality standard for conducting clinical trials

• Common Rule:

–US research guidelines

Tri-Council Policy Statement

For preschool children with mild to moderate visual acuity impairment, are glasses and patching effective in improving visual acuity, compared with glasses alone or no treatment?

• Research question:

–Is drug therapy associated with long-term morbidity and mortality in older persons with moderate hypertension?

P = Older persons with moderate hypertension

I = Drug therapy

C = Not stated  (presumably any intervention other than the named drug therapy)

O = Long-term morbidity and mortality

• Aka Kennedy-Kassebaum Act (1996)
• Consists of 5 titles
• Privacy rule:

–National regulations for the use and disclosure of Protected Health Information (PHI)

• Security Rule:

–Deals specifically with Electronic Protected Health Information (EPHI)

• Well-formulated questions determine:

–Criteria used to select studies

–Development of the search strategy

–Data to be abstracted

• Frame the question: figure out what your question is

–Patients, interventions, comparison group, outcomes

• Classify: what type of question is this and what is the best evidence to address that question?

• Done by searching literature, databases etc.

Principles:

• Generate appropriate keywords
• Choose database (e.g. Cochrane, Pubmed)
• Conduct the search (use Boolean operators AND, OR etc.)

Elements of the question

1.Frame the question you want to answer

–Consider patients /interventions /comparisons /outcome

–Classify the type of question

–Identify appropriate study designs to address question

2.Find the best evidence

3.Critically appraise the evidence

4.Apply evidence

Declaration of Helsinki (DoH)

• Basic principles:

–respect for the individuals and their rights, including the right to make informed decision

–subject's welfare must always take precedence over the interests of science and society

–ethical considerations must always take precedence over laws and regulations

• Assessment of the practicality of a proposed project or system
• Assessed by the SJSM Research Committee

–Usually during RHMI/RHMII Courses

• Feasibility analysis determines if research is

–technically feasible

–feasible within the estimated cost

will be profitable

Intervention

Outcomes

Population

condition

• Patient population
• Inclusion and exclusion criteria
• Exposure definition/intervention composition, dose, timing
• Comparison group/controls
• Management protocol (e.g., cointerventions) for trials
• Outcome definition (e.g., follow-up time, cause-specific
• mortality)
• Quality of design and execution
• Analysis

Formulating the Question: C

• For trials:

–Placebo

–Standard therapy

–No treatment

• For epi:

–No exposure

–Non-cases  (hospital, neighborhood, etc.)

Declaration of Helsinki (DoH)

–Research should be based on a thorough knowledge of the scientific background

–Risk and benefits should be carefully assessed

–Research should be conducted by suitably trained investigators

–Experimental investigations should always be compared against the best methods

Full name: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, Report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

Created by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

• Summarizes ethical principles for research in US
• Principles:

–Respect for persons (autonomy)

–Beneficence (“Do not harm”)

–Justice

• Independent reviewing body
• Functions:

–Evaluation of investigational protocols prior to research

–Validity and ethical integrity of research

–Accuracy of the informed consent

–Treatments and procedures do not present an undue risk

–Periodic review of the data so that a trial can be stopped

–

• Study cannot commence without IRB approval

50 yo m, with no risk factors comes to see you in your clinic and asks you whether he should take aspirin to prevent CV disease

• P: A healthy adult
• I: Aspirin
• C: No aspirin
• O: Cardiovascular disease
• T: In 5 years

Asking a PICO(T) question:

In an otherwise healthy man with no risk factors or medical conditions, what is the benefit of taking aspirin vs. no aspirin in preventing cardiovascular disease in 5 years?

• Well-formulated questions (and analytic frameworks):

–Determine final criteria used to select studies for review

–Which data will be abstracted

• Investigators should disclose sources of financing
• Financial disclosure is essential to help ensure an objective interpretation of research data

Formulating the Question: P

• Types of people (P)

–Define condition or disease, including explicit diagnostic criteria

–Population and setting of interest  (age, ethnicity, sex, community, hospital, outpatient)

Things to consider:

• How is the disease/condition defined?
• What are the most important characteristics that describe these people (participants)?
• Are there any relevant demographic factors (eg, age, sex, ethnicity)?
• What is the setting (eg, hospital, community etc.)?
• Who should make the diagnosis?
• Are there other types of people who should be excluded from the review (because they are likely to react to the intervention in a different way)?
• How will studies involving only a subset of relevant participants be handled?

Exposure

Outcome

Setting

Population

Each _____________ has five elements:

1.Domain  (eg, anxiety)

2.Specific measurement (s)  (eg, Hamilton Anxiety Rating Scale)

3.Specific metric (s)  (eg, change from baseline)

4.Method (s) of aggregation  (eg, mean, median)

5.Time point (s)  (eg, 3 months, 6 months)

• Generally not possible to formulate an answerable question without knowing a bit about what data are available
• Need to guard against testing a post hoc hypothesis

Formulating the Question: O

• Types of outcomes (O):

–Criteria for defining

–Important to consumers, providers

–Unpublished data?

Things to consider:

• Main outcomes, for inclusion in the 'Summary of findings' table, are those that are essential for decision-making, and should usually have an emphasis on patient-important outcomes.
• Primary outcomes are the two or three outcomes from among the main outcomes that the review would be likely to be able to address if sufficient studies are identified, in order to reach a conclusion about the effects (beneficial and adverse) of the intervention (s).
• Secondary outcomes include the remaining main outcomes (other than primary outcomes) plus additional outcomes useful for explaining effects.
• Ensure that outcomes cover potential as well as actual adverse effects.
• Consider outcomes relevant to all potential decision makers, including economic data.
• Consider the type and timing of outcome measurements.

• Private interests affect research process
• Ways to avoid

–Prevention

–Public Disclosure

–Follow Procedure

• Presenting someone else’s work as your own
• Regardless of the author consent
• May be intentional or unintentional
• Applies to text, graphs, illustrations etc.

• Applies to design and methods
• Findings represent research phenomenon
• Internal validity:

–Affected by flaws within the study itself

–Usually problems with design/research instrument

• External validity:

–Extent to which you can generalize your findings

–Eg, can you apply your findings to larger groups?

Topic: the association between the level of alcohol consumption and the incidence of stroke Research question: does moderate to heavy alcohol consumption reduce the risk of stroke?

• Population = adults without prior stroke
• Exposure = alcohol consumption presented in/could be converted to drinks per day; not solely binge or short term (24 hour); measured over> past 1 month or longer
• Comparison = non-drinkers
• Outcome = ischemic or hemorrhagic stroke or both; enough information to estimate RR, OR, AR, 95% Cls
• Design = cohort studies

Resources for how to frame your question

Formulate the Topic

• Confirm the need for a new review
• Develop an analytic framework
• Use a standard format to articulate each question of interest

–For example, PICO(TS)

• State a rationale for each question
• Refine each question

Patient or population at hand

Intervention or Exposure

Comparison

Clinical Outcomes

Additional elements: Time, Setting (eg, primary care, specialty, inpatients etc.)

• Fabrication, falsification, or plagiarism
• Fabrication

–making up data or results

• Falsification

–manipulating research data

–changing or omitting data

• Describe common issues related to research ethics (copyrights, plagiarism, publications, conflict of interest, research misconduct, validity, feasibility etc.)
• Explain the role of Institutional Review Boards (IRBs) in research process
• Describe approach to research process in SJSM