clinical investigation exam 2

in a _____ study design, the researchers do not assign intervention and ____ is from another factor

observational, exposure

in a ______ study design, participants are assigned to specific treatments

experimental

a _______ study design can be prospective OR retrospective where a ____ study design must ALWAYS be prospective

observational, experimental

non-controlled trials, controlled trials, and pragmatic trials are all considered ____ studies and have the most ________

experimental, investigator control

cohort studies, cross-sectional studies, and case control studies are all ________ and have less ________

observational, investigator control

what is considered the gold standard for trials?

r (andomized) c(ontrolled) t(rials)

______ is the comparison of two or more therapeutic treatments that are considered true therapeutic alternatives in real clinic practice

comparative effectiveness research

what does comparative effectiveness research intend to involve?

healthcare provider and the patient in the decision-making process

a non-controlled trial does not use a _____

control group

in a non-controlled trial, you cannot compare _____ between treatments

efficacy

the purpose of a controlled trial is to ____ and ______ differences in effects of interventions/treatments

measure, quantify

_____ is required by FDA before a new medication can be approved

controlled trial

in a controlled trial, you can determine ____ and _____, and measure the _____ of effect

efficacy, safety, magnitude

a controlled trial that is non-randomized is only considered reliable if confirmed by a ______

randomized trial

active control receives ____ treatment, placebo receives something that ___ it, and historical is data from ____ individuals who received the therapy

investigational, mimics, previous

what 3 situations are placebo controls useful?

no proven effective intervention, withholding standard treatment poses no risks, when response to established treatments and placebo are highly variable

when should placebos not be used because it might be unethical?

life threatening situation without active treatment, severe disease progression without active treatment, real world practices

_____ is when the control is an active treatment

active comparator trial

why would we use active controls (4 reasons)?

not ethical for placebo, compare experimental to alternative, drug has placebo effect, real world comparisons

efficacy treatments are use to see the performance of a drug under _______ and are also known as ______

ideal conditions, explanatory studies

effectiveness studies are done to see performance under _______ and are also known as ______

real world conditions, pragmatic studies

in _____ studies, cost, adherence, physician recommendation and access is not a problem, but it might be in ____ studies

efficacy, effectiveness

____ validity answers the research question, has reliable results, and related to quality of design where ____ validity is more meaningful to real world practice in patient care and results are more generalizable

internal, external

in efficacy studies, the intervention is often compared to a _____, it has strict _____ & _____ criteria, and use of _____ is restricted

placebo, inclusion, exclusion, concurrent medications

efficacy studies have high ____ validity and effectiveness studies have high _____ validity

internal, external

in effectiveness studies, the intervention is compared to _____ and commonly use _____, there is less strict _____ & _____ criteria, and patients can use _______

usual care, active controls, inclusion, exclusion, concurrent medications

in randomized control trials, subjects are ___ assigned into groups, interventions compared to ____, and outcomes are compared after patients receive _____

randomly, control group, intervention

what are 2 words to describe RCTs?

prospective, quantitative

if multiple interventions are being studied in a RCT, there will be more ____

groups

what are 7 components of an RCT?

question, hypothesis, outcomes, stats tests, experimental and control treatments, subjects, randomization

in efficacy studies, it is common to exclude _____, and inclusion criteria is for subjects who have ___ of interest

vulnerable populations, condition

what are 4 examples of strict exclusion criteria for efficacy studies?

organ dysfunction altering PK/PD, safety, comorbid conditions, unlikely to respond

statistical power is based off what endpoint?

primary

what endpoint is this an example of;

all CV events including heart attack, stroke

composite endpoint

______ effects cause beneficial outcomes where _____ cause harmful and dangerous outcomes

placebo, nocebo

placebo and nocebo effects result from a patients ________ of treatment and side effects

expectations

what is the statistical calculation that quantifies the size of the difference between treatments

effect size

the effect size tells you what 3 things?

magnitude, direction of effects, practical significance

the investigator must determine what size of difference between outcomes (effect size) is _____

clinically meaningful

a small effect size has _____ but a large effect size has _____

limited practical applications, some practical meaning

the effect size allows results to be compared with results of other _____ that used comparable measures, but only if they had similar _____

studies, design features

what is 4 ways to calculate effect size?

cohens d, relative risk, odd ratio, AUC

___is the number of subjects in a study and is calcualted based on the ____ in effect between groups

sample size, size of difference

what is 5 things that impacts the sample size?

study design, primary endpoint, effect size, acceptable error, expected variability

____ bias is when individuals in study differ from population of interest

selection

____ bias is when there is unequal loss of subjects in each group

attrition

___bias is then subjects answer inaccurately to question about past events

recall

___bias means subjects have met inclusion/exclusion criteria but not enrolled equally in groups

allocation

attrition, recall, and allocation bias are all examples of what?

selection bias

____bias is when recording info varies in systematic way based on individual making measurements

observer

selection bias limits ability to ______

generalize findings

what bias is this an example of:

enrolling subjects from a clinic but miss all those who didn’t seek care

selection

what are some factors that impact recall bias?

emotions, importance, time, beliefs, age, diseases, relationship with investigator

what are some examples attrition bias may occur?

adverse events, death, unsatisfactory response, noncompliant

what is the general rule of thumb for attrition bias?

<5% attrition leas to little bias but >20% threatens validity

allocation bias is when the investigators know what the next _______is

intervention

what is ways to minimize allocation bias?

blinding, opaque envelopes, central computer and pharmacy controlled randomization

observer bias arises from conscious or unconscious ____

prejudices

what are 4 ways to reduce bias in clinical trials and when should they be determined?

blinding, randomization, clear subject criteria, clear protocols, a priori

_____ randomization is when every subject has equal likelihood of being in intervention or control group

simple

_____randomization is when interventions are assigned within blocks of participants and subjects are assigned to ____ randomly until desired _____ are achieved

blocked, blocks, proportions

_______randomization is when subjects are divide into groups because of a confounding variable then randomized into intervention groups

stratified

t/f in blocked randomization, there could be different number of people in experimental and control

false

a ___ variable makes it hard to interpret relationship between variables because it has an effect on ____

confounding, independent and dependent variables

in a parallel study, the participants are treated equally except for the ____

intervention

in a crossover study design, there is a _____ to clear drug from body and each subject receives _____

washout period, all interventions

what are 2 ways you can compare results in a cross over study design?

between groups, between treatments in a group

a study with a _____ period can help increase proportion of subjects who comply with study protocol

run-in

for a study with a run in period, all subjects are treated with ____ for a set period of time and those who comply are ______

intervention, randomized

blinding/masking reduces ____ and ____ & ___ effects

bias, placebo, nocebo

if the trial is ____, all persons involved are aware of the treamtent

no blind

a ___ trial is when only subjects are unaware of treatment, ____ is when subjects and investigators are unaware, and ___ is then subject, investigators, and data interpreters are unaware of allocation

single blind, double blind, triple blind

a _____ design for a trial is a technique to maintain blind when treatments can not be made identical

double dummy

if each subject in a trial receives two treatments, group a receives active pill and placebo cream but group b receives placebo pill and active cream, this is an example of ____

double dummy design

what can make it difficult to mask/blind?

identifiable attributes, side effects, surgeries

why type of crossover design is the most comon?

2×2

in a crossover study design, the time of treatment administration is the ____ and the assigned order of interventions is the _____

study period, study sequence

what is randomized in a crossover study design?

the order of treatment

what is important in a crossover study design regarding the treatments?

must be independent

what are 4 advantages of a crossover study deisgn?

higher power and statistical efficiency, more data, each subject is a control, within subject variability less than between subjects

what are 4 disadvantages of crossover study designs?

subject condition must be stable, studies are longer, subject recruitment and retention is hard, hard to handle dropped or missing data

what is 5 things to consider in crossover study designs?

treatment sequence, timing, sample size, stats analysis, dropouts

what is a time dependent crossover study?

crossover will occur after a specific time of treatment

what is a disease state dependent crossover study?

crossover after control of symptoms is achieved

t/f the timing of the crossover should not be blinded

false

the ____ effects in a crossover study is when the subject’s conditions has changed between 1st and 2nd period and therefore are not in the same condition at the beginning of each, possibly because of disease progression

period

the ____ effects in a crossover study is when the treatment order alters the results

sequence

the ____ effects in a crossover study is when the therapeutic effect carriers over OR drug is still present in the body

carryover

what are 2 examples of causes of the period effect?

drug resistance, disease progression

what period(s) does the sequence effect affect?

1 and 2

What is 2 examples of what causes the sequence effect?

weight loss drug vs placebo, conditioned learning response

t/f the carryover effect only affects the second period

true

in carryover effects in a crossover study, the outcomes may be from what 2 things

result of treatment 2 and/or residual effects of 1st treatment

the washout period must be long enough for ____ & ____ to return to baseline

physiologic effect, drug level

how many half lives does it need to be in the washout period to assume complete elimination

5

t/f the washout period must be long enough for both treatments

true

what are 5 appropriate conditions for a crossover study?

bioavailability, stable conditions, cannot be curable, rapid response, not long lasting treatment effect

when is crossover not appropriate?

curable disease, condition cannot be replicated, crossover effect is likley

what 3 things can encourage a crossover effect?

long pharmacologic effects, long half life, physiologic effects

hypertension and diabetes are ____ for crossover studies where cancer, depression, and stroke are ______

appropriate, inappropriate