Lecture 25: Overview of Research Methodology Flashcards Preview

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Primary Research Question

– The one the investigators are most interested in answering
– The question on which the sample size of the study is based
– The outcome that must be emphasized in the reporting of results


Secondary Research Question

– Related to the primary question but are “less important”
• Explore a different outcome than the primary question
• Explore a different patient subgroup

Is drug effective (primary) and safe (secondary)


what research do clincians encounter most?

phase 3 or 4

typically most helpful for clinical decision making.


describe pre-clinical research

In vitro or animal studies

molecules to be tested to determine efficacy and safety

15-20 year process


describe Phase 1

Human pharmacology studies: drug tolerance, metabolism, interactions, pharmacokinetics, pharmacodynamics, dose finding

tests how we move from tube to pts, how body tolerates with healthy volunteers


describe Phase 2

Therapeutic exploratory studies: effects of various doses, surrogate (biomarker) outcomes

research for group of small patients, surrogate endopoint trials come into play, effect of a med on biomarkers or lab tests


describe Phase 3

Therapeutic confirmatory studies: demonstrate clinical use & establish safety profile.
– “Prospective studies comparing the effects and value of interventions() against a control
in human beings.”

prove drug is beneficial, safe, efficacious for a large pop


describe Phase 4

Therapeutic use studies: examine drug in broad or special populations, seek to identify uncommon adverse events.
– ”Long term studies or studies conducted after regulatory agency approval of the drug or device”

on market, look at special poplations (Chronic kidney disease), uncommon AE


what is the 1st q to ask to decide what type of study should be used?

descriptive (PO) vs analytic (PICO)

Q1: was the aim to describe a population (PO) or quantify the relationship b/w factors (PICO)
Quantify relationship b/.w exposure and outcome (drug and effect) = analytical type of research


what is the 2nd q to ask to decide what type of study should be used?

analytic - experimental vs observational analytic

Was the intervention allocated randomly?
- Randomized to active treatment and control, cross over studies
- Observational research: if not being controlled by research and not randomly assigned
○ Cohort vs cross sectional and case control studies


what is the 3rd q to ask to decide what type of study should be used?

cohort vs cross sectional vs case control study

Q3: when were the outcomes determined in relation to exposure we are trying to determine (after, same time, before exposure)
- Cohort study: AFTER the exposure
- Cross sectional (analytic): exposure and outcome AT THE SAME TIME
- Case Control Study: looking at outcome and know it before the information about exposure is available; identifying cases who we know have outcome of interest and look back to see whether or not they've had exposure in the past


look at Oxford levels of evidence

Level 1: therapy related qs with systematic reviews or randomized systemic revies
Level 2: RCT
L3-4: Cohort study or control study
Level 5: mechanism based reasoning

Similar RCTs, sometimes only have observational research, not ethical to expose someone

If asking about how common a problem is, we won't do a RCT, but survey or census


what are fundamentals to a study?

smoking cessation example

Exposure: early NRT nicotine replacement therapy
- Usually for course of 12 wks
Outcome: did the subject quit

Must include a comparison

Research q: In smokers, does NRT started 2 wks prior to the quit date improve cessation rates at 6 months

Quit rate is outcome

Revised research q: in smokers, does early NRT in comparison to NRT started on the quit date improve cessation rates at 6 months or 1 year


define confounding variable

“A variable other than the risk factor & outcome variable under study which is related independently to each of the other two and can create an apparent association or mask a real one.”

smoking, coffee and cancer

Randomized experimental studies will control confounding variables


observational vs experimental (randomized studies)

1. Observational Studies
– No manipulation of study groups
• Only observe patients and outcomes
– Good for questions relating to harm (causation)

2. Experimental (Randomized) Studies
– Comparable to Cohort studies EXCEPT the exposure is determined by
the researchers
• Follow the 2 groups to see who has outcome of interest
– Good for questions of therapy/prevention


Randomized Controlled Trials


The goal of a randomized controlled trial is to make exposed and control similar in all respects other than the intervention at the start of the study and maintain that balance as the trial progresses.

defined pop gets new treatment or control/current treatment
- outcome with disease or no disease

Exposure is determined by the researchers
– Researchers expose one group to a therapy & not the other group
– Then follow the 2 groups to see who has outcome of interest


Randomized Controlled Trials

strengths and weaknesses

• Gold standard to answer “therapy” or “prevention” questions
• Strengths
– Low susceptibility to bias vs. other designs
– Why? reduce confounders
• Weaknesses
– Expensive & time consuming
– Less generalizable (i.e., less applicability)
– May introduce “hidden bias”


efficacy vs effectiveness research
which does RCT does?

efficacy: does treatment work under ideal conditions?

effectiveness: does treatment work under ordinary circumstances?

RCT gives efficacy rather than effectiveness


Superiority RCTs

Superiority trial to show one intervention is better than another

– Most common RCT done
– Comparator most often is placebo
– Assesses whether the new intervention is better or worse than control
– Aim to rule out equality between treatments


Equivalence or Non-inferiority RCTs

Equivalence: show tha 2 drugs are same in terms of effectiveness and efficacy

Non-inferiority: New drug is no worse than an existing gold standard

– Sometimes it is unethical to do a placebo controlled RCT
– Aim to rule out differences between two treatments


“Quasi Experimental” Designs

– Definition: look like experimental design but lack true randomization
but there is some aspect of randomization


Cohort Studies


group of pts

exposed or not exposed

do they develop disease or not?

Randomization is not the process of detemrining when ppl are exposed or not exposed

Ppl are exposed because a pt decides to take an otc or hcp recommended


prospective vs retrospective study

Prospective study that happens forwardf in time, in the future
- Not always feasible

Prospective study that happens forwardf in time, in the future
- Not always feasible
- Retro uses data that is already collected like in a pt med record or alberta health services
- Define a cohort back in the past to see whether there are ppl exposed to a certain med and see if they got an outcome of interest


Cohort Studies

When are they used?

• Used when it is not reasonable to expose people to something
• Can be used to answer questions about causation (therapy)
• Good for answering questions about prognosis
- harm questions, can be therapy tho not highest level of evidence

Inception cohort: group od people with same in disease, stage, early in disease
Follow them in time


Cohort Studies

what are they

• Two or more groups of people are selected
• Basis for selection is EXPOSURE to a particular agent
– (e.g., Occupational exposure, environmental toxin)
• Groups are followed-up to see how many develop the outcome of interest

Key Points
• Hallmark is the comparison of EXPOSED to NON-EXPOSED
• No intervention – Only observe patients during course of study


Case-Control Study


Associations b/w exposure and outcome rather than starting with exposure status

Outcome determined first; recall exposure

study group - identify cases or controls

determine if they were exposed or not exposed previously


Case-Control Study

When are they used?

• Generally concerned with establishing the causes of disease
• Usually the only option for studying rare conditions

key pts
• People are selected on the basis of outcome/disease NOT exposure
• Cannot demonstrate causality, just associations


Case-Control Study

what are they?

• Type of retrospective observational study
• Identify a group of people with a disease of interest (cases) and
compare them to a similar group of people without the disease
• Data are then collected on past exposure to a possible causal agent
for the disease


Cross - Sectional Survey

what are they?

– A representative sample of participants is recruited
– They are interviewed, examined or otherwise studied
– Defining feature: data collection at a single time point
• e.g. What do first year students think about PHARM 324?
• e.g. What is the prevalence of Peripheral Arterial Disease in adults over
the age of 50 in Alberta?1


Cross - Sectional Survey

advantages, disadvantages

simple, cheap

no causation

Hopw prevalent is a disease
Sample survey: we get some people
Census survey: everyone in populaiton

Cannot look at causation