RHM-1 Intro

PICO method:

C O

Describes trends, cheap, easy

• 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

• 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)

Not all studies provide adequate data. Disadvantage.

• 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

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

• 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.

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

Only subjects are blinded to the treatment or intervention they receive

• 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

• Researcher and participants are both aware of the treatment intervention

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

Direct participation of authors

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

• 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

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

Small group of similar cases

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

PICO method:

P

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

Both subjects and investigators are blind to the treatment or intervention

PICO method:

I

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).

Greatest statistical power

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

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

–Critical appraisal skills program (CASP)

–“Levels of evidence”

“Strength of recommendation

Summarizes primary research sources, eg reviews, meta-analyses

• ‘‘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

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

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

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**

PICO method:

C

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

Represent the highest level of evidence.

PICO method:

T