drug lit - RCT :) Flashcards

Question

Double-Blind

Answer 1

_participants__ and _researchers unaware of treatment allocation advanatge Bias from participants and investigators reduced (more rigorous) Improves internal validity disadvanatge Potential for unblinding - because the side effects may be evident Resource intensive

Answer 2

___participants____ and researchers and data-assessors (outcome assessors) unaware of treatment allocation advantage Bias from participants and investigators and assessors reduced (most rigorous) Improves internal validity disadvantage Potential for unblinding Resource intensive

Answer 3

C Triple-blind - correct :)

Answer 4

Recruitment methods Incentives Target own patients - MGH may recruit their own patients Advertisements Other sources - physician referrals Enrollment can impact internal and external validity Internal validity - Too few patients = underpowered Selection bias - Subjects that meet inclusion/exclusion criteria are not enrolled Examples: - Only enroll patients that will be adherent, may overestimate efficacy - Only enroll patients they perceive will do well

Answer 5

Not representative of the target population Underrepresentation of minority populations

Answer 6

____________: participant demographics that must be present in order for the person to be enrolled into the trial Should match population being studied Defined objective criteria ____________: characteristics that prevent a participant from enrollment into the trial - Patients at risk or who have confounding variables - Special populations (pregnancy, cancer, children, etc.) - Risk of adverse events, contraindications to study drug - Characteristics that alter pharmacokinetics (movement of the drug) (renal/hepatic function) Important for extrapolation (generalization) of results to general population (_external validity___________) Subjective inclusion/exclusion criteria lowers _our internal validity___________

Answer 7

The person or system responsible for randomizing people to the intervention or control group: - Does not know what the next treatment allocation will be and - Conceals the results of the allocation from others Allocation concealment is not the same as blinding - Allocation concealment is preventing the knowledge of the randomization sequence - Blinding is preventing the knowledge of treatment assignments once participants are randomized Minimizes risk which increases internal validity - investigator cannot influence group assignments - Minimizes chance of blinding being revealed Methods of allocation concealment - Centralized randomization done with an automated computer system or off-site statistician - Interactive Voice Response Systems (IVRS) - Interactive Web Response Systems (IWRS) - Centrally controlled - Pharmacy controlled - Sequentially numbered opaque sealed envelopes (SNOSE) Not concealed if: - Non-opaque, non-sealed envelopes - Investigator controls allocation - Any method where the investigator or participant is aware of the allocation scheme or pattern Allocation concealment is a different concept to blinding. It means that the person randomising the patient does not know what the next treatment allocation Note that allocation concealment is completely different from blinding. The allocation seeks to eliminate selection bias during the process of recruitment and randomization, whereas blinding seeks to reduce performance and ascertainment bias after randomization.

Answer 8

False - correct

Answer 9

C Investigator control - correct

Answer 10

Intervention - Therapy under investigation comparator Therapy used as a comparison to intervention - Placebo - Active control - Another medication - Medical intervention Historical data

Answer 11

Used when comparing different dosage forms or frequencies Two different placebos used to maintain blinding Example Intervention: IV active drug, placebo oral medication Comparator: IV placebo, active oral medication

Answer 12

Study phase in which the medication is slowly increased (given) to: Minimize side effects Reach a certain affect Blood pressure INR Etc.

Answer 13

Phase completed by participants prior to their enrollment in the study Usually brief (2-4 weeks) Placebo run-in (also known as a washout period) Washes out effects of prior treatments Active run-in Assess adherence Adverse events Participants that do not meet prespecified criteria Need to determine if run-in phase leads to selection bias Ancillary treatments Treatment allowed outside of defined groups Some participants may receive Often needed for ethical reasons (_strength) Based on “judgement” of physician (__weakness__________) Leads to differences between groups (_weakness___________) Confounding variable (_weakness___________) Adjunctive treatments Treatment given to both groups Often needed for ethical reasons (_strength___________) Not a confounding variable (_strength___________)

Answer 14

Duration needs to be long enough for outcome to appear Too short = lowers internal validity Too long = may lower external validity Very rare Planned vs. actual duration Early termination Usually due to ethical reasons Consider impact on results _weakness___________: termination results in inability to rely on results _neutral/strength___________: despite early termination, had statistically significant results

Answer 15

Authors required to disclose source of funding and conflicts of interest Sources of funding: Pharmaceutical industry University medical centers Nonprofit foundations Government agencies Pharmaceutical industry funding Necessary for new medications Evaluate involvement in: Study design Data monitoring and analysis Manuscript preparation

Answer 16

How/when participants were followed Monitoring occurs at predetermined intervals Data collection method determined before trial starts Should be consistent/feasible in clinical practice Relates to external validity___________ Should be the same for all participants Relates to _internal validity___________ Objective monitoring parameters (_strength___________) Measurable Subjective monitoring parameters (_weakness___________) Self-reported Potential for ____________: a systematic error that occurs when participants do not remember previous events or experiences accurately or omit details Adherence Should match practice (80% = _strength___________) Sometimes manipulated or controlled (_weakness___________) Data and Safety Monitoring Board Part of some larger trials Members of board blinded to treatment allocation

Answer 17

Primary endpoint Prespecified outcome that directly addresses the hypothesis of the study The basis of trial design, including sample size, power analysis, etc.

Answer 18

Examined if the primary outcome is statistically significant Trial is _not powered___________ to secondary endpoints Interpret with caution Should not base clinical decision on this

Answer 19

Disease oriented evidence (DOE) Nonclinical evidence that addresses factors that do not have a direct impact on patients E.g., cholesterol levels, HbA1c Do not always correspond to the _morbidity or mortality___________ results that were presumed Patient oriented evidence (POE) Measures outcomes that patients care about E.g., quality of life, quantity of life Patient oriented evidence that matters (POEM) Outcomes that patients and clinicians care about E.g., cardiovascular events, vision loss, kidney failure, quality of life

Answer 20

singular coprimary composite surrogate

Answer 21

One primary endpoint advantage: Simple Statistically efficient Reduced sample size disadvantage: Incomplete assessment Risk of misinterpretation

Answer 22

Two or more primary endpoints of equal importance advantage: Useful if demonstration of two or more outcomes is necessary to establish clinical benefit More comprehensive Address multiple objectives disadvantage: more complex to interpret Increased risk of _type ii error (saying that there is no difference hewn it really does exist - false negative)__________ Increased sample size requirements

Answer 23

A combination of two or more individual endpoints into a _single outcome measure___________ Purpose: capture a broader array of clinical events, provide a comprehensive assessment of efficacy, or enhance statistical power advantage: Increased overall event rate Efficient disadvantage: Complicated interpretation Risk of misinterpretation Effect often smallest for most important component and largest for less important components Must look at individual components to see what is __________ statistical significance Prone to post-hoc analyses

Answer 24

A substitute or proxy measurement advanatge Quick Inexpensive disadvantage Risk of misinterpretation May not predict clinical benefit Must be validated

Answer 25

D Blood pressure - correct

Answer 26

C Composite endpoint - correct :)

Answer 27

adjudication = verification Important in trials with clinical outcomes Reduces risk of bias that can occur when the interpretation of results is different with different medical providers Third party blinded to treatment allocation that verifies that an outcome has occurred

Answer 28

See Biostatistics class notes for information pertaining to: Variables Descriptive statistics Alpha (α), type I error, p-values Beta (β), type II error, power Confidence intervals Calculations: ARR, NNT/NNH, RRR/OR/HR, RRR/RRI

Answer 29

intention-to-treat (ITT) Analysis _all patients___________ randomized are included in statistical analysis Accounts for loss to follow-up, death, lack of adherence, treatment failures, etc. High external validity Gold standard for RCT Strength

Answer 30

All patients randomized that received _at least 1 dose___________ of study medication are included in statistical analysis High external validity Strength

Answer 31

Only patients that _completed treatment___________ are included in the statistical analysis May overestimate efficacy and underestimate safety Low external validity (weakness) Helpful if used as a sensitivity analysis to verify ITT results (strength)

Answer 32

Terms used to describe the timing and nature of decisions related to data analysis or hypotheses A priori Decisions and hypotheses that are established __before__________ the data is collected or analyzed Strength More robust Less prone to bias Helps control for type I errors (false positive) E.g., primary and secondary outcomes, sample size calculations, statistical analysis plans

Answer 33

Decisions and analyses made _after___________ the data has been collected and without pre-established plans Weakness More susceptible to biases, as researchers may be influenced by the observed data Overinterpretation or introduction of false associations Inflated risk of type I errors Hypothesis generating Statistical tests

Answer 34

number of groups: 1 _normally distributed___________ number of groups: 1 __one sample test or dependent/paired t test__________ number of groups: 2 (intervention and comparator) _independent/unpaired student t-test___________ number of groups: >3 __anova__________ or

Answer 35

number of groups: 1 __chi-squared test__________ number of groups: 2 (intervention and comparator) _chi-squared___________ or

Answer 36

Participants Baseline characteristics reported in results section Internal validity Similar baseline demographics Strength External validity Generalizable to strrenghth

Answer 37

Comprises 25-item checklist and a flow diagram for transparent reporting of clinical trials (strength) - what happens to the people as they go through the trial Flow diagram Assess reasons for withdrawal Impacts external validity Rule of thumb At least _80%___________ of the study participants should complete the study/be included in analysis (strength)

Answer 38

Statistical significance p value If p is < alpha, results are statistically significant Confidence interval (CI) If confidence interval does not include the value of no difference, results are statistically significant Continuous endpoint: 0 = no difference Dichotomous endpoint: 1.0 = no difference

Answer 39

Continuous data: Evaluate absolute difference between groups Upper and lower ends of 95% CI Dichotomous data: Evaluate the HR/OR/RR Calculate the RRR (1- RR), ARR (%intervention - % control), NNT/NNH Upper and lower ends of 95% CI Benefits versus risks Consider: burden of administration, adverse events, cost Compare to existing data

Answer 40

Discussion Authors’ interpretation of results Comparison to previous data Strength and limitations of the study Highlight unexpected results Explanation of how results add to current data

Answer 41

No new data should be introduced Concise overall summary of findings Conclusion must be consistent with the data

Answer 42

Impact of trial on clinical practice Questions to ask about the trial as a whole: What are the strengths? What are the weaknesses? Can the results be applied to the general population with this condition? Will the results of this study change practice? Why or why not? Does this trial provide strong/moderate/weak evidence for/against the intervention? Consider Statistical significance Clinical significance Internal/external validity Feasibility of treatment Resources to use when determining the application Clinical expertise Journal article editorial Previous data DynaMed Medscape Pharmacist’s Letter Experts in the field