RHM-1 Intro

Advantage: Some evidence of causality, multiple outcomes of a single exposure

Disadvantage: Expensive, inefficient for rare outcomes, require long term follow-up or  large population, cannot control unmeasured confounders

Incidence, RR, OR**

Not all studies provide adequate data. Disadvantage.

• ‘‘Garbage in-garbage out”

–A meta-analysis is only as good as the studies in it

–Narrower confidence interval around combination of biased studies worse than the

–biased studies on their own

–Beware of reporting biases

• “Mixing apples with oranges”

–Not useful for learning about apples, although useful for learning about fruit!

–Studies must address the same question

• Though the question can, and usually must, be broader

• MC design in clinical research
• Clinical study with 2 groups of treatment

–One group receives treatment A

–Another group receives treatment B

Greatest statistical power

• Aim: causality between exposure and disease
• Observation of 2 healthy groups of subjects over time

–One group is exposed to a specific substance

–Another group is not exposed

–Frequency of expected outcome is recorded

• Relative risk: statistical parameter used in cohort studies

Advantage:

Greater statistical power, confirmatory data analysis

Greater ability to extrapolate to general population affected

Considered an evidence-based resource

Disadvantage:

Difficult and time-consuming to identify appropriate studies

Not all studies provide adequate data for inclusion and analysis

Requires advanced statistical techniques

Heterogeneity of study populations

• Each subject receives the intervention and control treatment in random order
• Intervention and control treatment are separated by a washout period

Disadvantages: Expensive, time-consuming, lost to follow-up.

Advantages: Measure causality, controls unmeasured confounders.

Statistics:** RR – relative risk, OR – odds ratio

Only subjects are blinded to the treatment or intervention they receive

Levels of Evidence and grades ( Level 1-5. Level 1 - highest and most trustworthy)

• Method to determine clinical value of a study
• Principle: some articles are more persuasive

A (good) 1a 1b Systematic review of RCTs Individual RCTs

B(fair) Systematic review of cohort studies, Individual cohort study, Systematic review of case-control study, Individual case-control study.

C(conflicting) case series

D(bit sufficient) Expert opinion or bench research

Individual cohort study

Systematic review of case-control study

Individual case-control study

PICO method:

C O

• Focuses on a specific question
• Uses explicit, pre-planned scientific methods to identify, select, appraise and summarize similar but separate studies

• Test for validity, reliability and clinical relevance
• Tools for appraising research articles:

–Critical appraisal skills program (CASP)

–“Levels of evidence”

“Strength of recommendation

• OPTIONAL component of systematic reviews
• Statistical method
• Combines data from several studies to integrate findings
• Possibility depends on “combinability” of studies
• Greater statistical power

Direct participation of authors

Types: interventional (experimental) and non-interventional (observational)

Describes trends, cheap, easy

Advantage: Rare outcomes, work backwards (outcome → exposure), can generate hypothesis (multiple risk factors explored)

Disadvantage: No causality (questionable relationship), selection bias, recall bias, no incidence or prevalence

Statistics: OR

PICO method:

I

• Retrospective cohort

–Investigators start with disease

–“Go back in time” to detect exposure

• Prospective cohort:

–Investigators start with exposed and unexposed groups

–Determine whether disease later occurs

Advantage: Fast, inexpensive, no loss to follow up, associations can be made

Disadvantage: Cannot study causality, cannot study rare outcomes, selection bias, self-reporting bias, response bias

Statistics: Prevalence

• Researcher and participants are both aware of the treatment intervention

PICO method:

T

Represent the highest level of evidence.

PICO method:

P

• Intervention or exposure
• Comparison
• Clinical Outcomes
• Additional element: Time

Small group of similar cases

• When more than one study has estimated a treatment effect or association
• When the differences in the study characteristics are unlikely to affect the treatment effect (or when investigating specific differences)
• When the treatment effect have been measured and reported in similar ways (or when the data are available)

• Method of blinding where both groups may receive placebo
• Used when 2 treatments cannot be made identical

• CER is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care
• The purpose of CER is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels

Summarizes primary research sources, eg reviews, meta-analyses

Both subjects and investigators are blind to the treatment or intervention

• Measure intervention effect
• Randomly assign individuals to an intervention group or control group
• Strongest study to determine cause-effect relation

• Investigators start with diseased and controls
• They “go back in time” and determine whether exposure occurred

study that compares patients who have a disease or outcome of interest (cases) with patients who do not have the disease or outcome (control participants) and looks back retrospectively to compare how frequently the exposure to a risk factor is present in each group to determine the relationship between the risk factor and the disease.

Eg, one group may receive treatment A and the placebo of treatment B, the other group would receive treatment B and the placebo of treatment A

Treatment consists of Drug A and indistinguishable Placebo A; drug B and indistinguishable placebo B. Patients then take either treatment A (Active drug A and placebo B) or treatment B (active drug B and placebo A).

PICO method:

C

• Observation at 1 specific point in time
• Usually subset of population/all population
• Determine prevalence of a problem