Lecture 6, part 3

Question 1

Reasons for non-compliance?

Answer 1

Toxic reactions to the tx
Waning interest, desire to seek other therapies
Inability to meet the demands of the study
Dz progression, co-morbidities, death

Question 2

Methods of enhancing compliance

Answer 2

Keep tx regimens simple and easy to follow
Enroll motivated and knowledgeable participants with fairly organized lives
Provide realistic picture of tasks involved during the informed consent process
Obtain detailed medical hx and reject ppl who seem unlikely to comply
Mask subjects to tx assignment
Maintain frequent contact
Conduct run-in or lead-in period
Offer incentives

Question 3

Primary outcomes should be selected to be what?

Answer 3

Easy to diagnose or observe and clinically relevant
Free of measurement or ascertainment error
Capable of being observed independent of tx assignment

Question 4

What aspects of the outcome can be measured?

Answer 4

Outcomes can be surrogates for actual phenomena of interest
Measure potential adverse effects

Question 5

Measurement of outcomes should have what characteristics?

Answer 5

Accurate and precise
Objective rather than subjective

Question 6

Masking definition

Answer 6

A tool used to create comparability with respect to post-randomization observations

Question 7

What is the goal of masking?

Answer 7

Prevent biased ascertainment of the outcome measure

Question 8

Types of masking

Answer 8

Single
Double
Triple

Question 9

Single masking

Answer 9

Participant doesn’t know tx assignment

Question 10

Double masking

Answer 10

Participant and investigators making the tx assignments are unaware of tx assignment

Question 11

Triple masking

Answer 11

Participant, investigators making the assignment, and investigator measuring the outcome are all unaware of tx assignment

Question 12

Aspects on ongoing monitoring

Answer 12

Need to monitor continuously
Evaluate safety/unanticipated effects at baseline and pre-specified periods throughout study
Findings (positive or negative) may necessitate early termination of the trial

Question 13

Aspects of intent-to-treat analysis

Answer 13

All individuals randomly allocated to a tx are analyzed as receiving that tx, regardless of whether they actually complete or receive the tx
Preserves baseline comparability of the groups for known and unknown confounders
Maintains the statistical power of original study pop
Unbiased results
Gives info on effectiveness of a tx under nl practice conditions

Question 14

Aspects of efficacy analysis

Answer 14

Determines the tx effects under ideal conditions if adherence to tx is perfect
Analyze the outcomes of those who complete tx in each group (ignore outcomes of those who failed to complete assigned tx)
Potential for bias as compared groups may no longer be similar (lose the benefits of randomization in terms of comparability)

Question 15

How to create comparability

Answer 15

With the respect to the tx experience: use of placebos, similar tx regimens
With respect to the participants: heterogeneity, randomization
With respect to post-randomization observations: masking or blinding of participants and researchers

Question 16

Issues with experimental studies

Answer 16

Exclusive study pop criteria limits generalizability of results
Focus on testing outcomes under ideal situations measures efficacy of the tx/intervention, not actual effectiveness

Question 17

Reasons to do randomized control trials

Answer 17

Arguably the only study design that can “prove” causation
Most influential to clinical practice
Provide the strongest evidence in “evidence-based” medicine
Required by FDA and other agencies for new drugs and some new devices
Often required by third party payers
Best for studying therapeutic interventions

Question 18

Reasons not to do randomized control trials

Answer 18

Expensive and difficult to fund - typically cost $100s of millions and take yrs to perform
Limited in scope- typically only answer a single question
Limited in generalizability - may not apply to most pts in practice
Logistically complex- usually involve multiple different clinical centers
Ethical considerations/constraints

Question 19

Practical issues to consider with experimental studies

Answer 19

Randomization to reduce bias
Recruitment of willing/eligible participants
Generalizability of participants/results
Participant noncompliance
Participant attrition
High costs

Question 20

How many clinical trial phases are there?

Answer 20

4

Question 21

Lab studies- definition and timing

Answer 21

Pre-clinical studies conducted in laboratories or with animal models
Usually take several yrs

Question 22

Details about phase I trials

Answer 22

Clinical pharmacological studies
Small sample of 20-80 participants (usually healthy)
Used to assess safety issues related to new drug or tx
-Safety and safe human dosage ranges (tolerable limits), toxicity and side effects

Question 23

Details about phase II trials

Answer 23

Clinical investigations of 100-300 pts
Evaluates the efficacy of the new drug or tx
Further assess relative safety

Question 24

Details about phase III trials

Answer 24

Large-scale randomized controlled trials of 1,000-3,000+ pts
Assess effectiveness and relative safety
Usually multi-center recruitment
Once a tx/drug passes this phase, it can be approved and licensed for marketing

Question 25

Details about phase IV studies

Answer 25

Monitor long-term (over several yrs) safety and effectiveness of new drugs/txs as they come into general use by the public
-AKA post-marketing surveillance
Not randomized studies, but can examine the effects of the drug in pops or situations not studied before

Question 26

Rationale of phase IV studies

Answer 26

Certain adverse effects may not become manifest for many yrs, or may be so infrequent that they may not be detectable even in relatively long RCTs