Vadheim: Non Randomized Controlled Trials

Front 1

when can nonrandomized trials be used and why?

Back 1

post licensure to monitor longterm effectiveness and safety because a potentially valuable treatment can not be withheald as a control; also used when it is unethical to randomize subjects to an exposure; it is not feasible to do a randomized trial

Front 2

nonrandomized trials take into account which of patients' rights

Back 2

1) the right to receive new and potentially better therapies
2)the right to safe and proven effective therapies

Front 3

nonrandomized prospective study design

Back 3

screen for treatment/exposure

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prospective study

Back 4

analytical study that begins with subjects in several risk categories and follows them over time to determine outcomes
lab experiments, RCB, cohort studies (concurrent cohort studies, historical cohort studies)

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cohort study design

Back 5

internal controls; study exclusion criteria; screen for treatment/exposure

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cohort study design

Back 6

screen to eliminate those who already have outcomes

Front 7

biases associated with exposures based on patient interview and history

Back 7

1) reporting bias
2) recall bias

Front 8

what phases of clinical trials use cohort studies and why?

Back 8

Phases I, IV, and V
Phase I: subjects cannot ethically be randomized to control or treatment because not enough is known about the effects of the drug; historical controls or self-controls are used
Phases IV and V: cannot withhold a licensed therapy; results are compared with historical results, subjects who had a different therapy, provider groups who dont offer the new therapy, etc.

Front 9

When otherwise is a cohort study useful in biomedical studies other than clinical drug trials?

Back 9

when an association between a risk factor and disease seems apparent; exposure to the risk factor is not ethical or practical; toxic exposures, recreational drugs, dietary factors, natural phenomena, unintentional medical exposures

Front 10

what type of cohort study provides the most definitive clinical evidence?

Back 10

cohort studies with internal controls`

Front 11

how do cohort studies with external controls screen?

Back 11

they use a source pop of possible treatment/exposure and possible nontreatment/nonexposure and screen to confirm treatment or exposure

Front 12

what are the characteristics of good control groups

Back 12

the similarity to the exposed group; similarity in demographics, health, geographic location, and time

Front 13

what types of controls might be used in nonrandomized clinical trials?

Back 13

controls from other source pops (diff clinics or hospitals, diff occupational groups, general population); historical controls (same popualtion but from the past); controls from the literature

Front 14

strengths of the cohort design

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allows study of exposures that cant be studied with RCB
allows complete description of drug effect natural history
permits studies of dose response
permits study of multiple outcomes
allows calculation of rates of various outcomes for diff doses and comparison with unexposed controls
exposure precedes effect
limits exposure ascertainment bias because screened a priori for exposure

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weakness of cohort study design

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large number of subjects
expensive
long duration of follow-up possibly (hard to do; lost subjects; results may be irrelevant by the end; subjects may change their exposure group over time)

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1 major weakness of cohort design

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difficult to control confounders and other extraneous variables that influence study

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biases associated with follow-up in prospective studies

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1) surveillance bias
2)lead-time bias
3)survival bias
4)response bias
5) observer/diagnosis bias

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surveillance bias

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unequal intensity of follow-up because of prior knowledge of exposure status

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lead-time bias

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subjects in one group diagnosed with outcome earlier in the disease process due to diffs in follow-up intensity of in the diagnostic procedures used

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survival bias

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unequal follow-up due to losses from competing causes of death

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response bias

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unequal follow-up because of subjects lsot to follow-up

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observer/diagnosis bias

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assessmetn of outcomes altered by prior knowledge of exposure status; or different assessment methods/persons for exposed and unexposed groups

Front 23

what are the measures of risk/protection in prospective studies; what can be measured

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1) incidence (absolute risk)
2) relative risk
3) risk ratio

Front 24

what are prospective studies often used to predict

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survival

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what is the central challenge of prospective studies

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follow-up data is often censored,

Front 26

what is kaplan-meier analysis used for?

Back 26

to describe and estimate and interpret survival characteristics; allows median survival time, survival proportiona t each observed time point,etc.

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what is log-rank test used for?

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to compare survival in different groups

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what is the Cox regression model used for?

Back 28

to assess the effects of different factors on survival time

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cox proportional hazards regression

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1) is the standard for complex survival analyses in biomedical research
2)allows analyzing the single and/or combined effect of several risk factors on survival
the probability of the endpoint is called the hazard
produces: baseline hazard/survival characteristics, estimated survival functions, relative risks for individual prognostic factors

Front 30

what benefits limitations and info can historical cohort studies provide?

Back 30

can provide scientific evidence about exposures from the past
permit longterm followup after exposure
are limited to exposures with good documentation
may be hampered by lack of information about potential confounders
have all the lost to followup problems