Lecture 7

Question 1

All clinical trials in the US must be registered where

Answer 1

Clinical trials.gov. Maintained by national library of medicine.

Relatively new- first available in 2000

Question 2

What to balance when choosing a sample size

Answer 2

Limit cofounding variables but keep study generalizable to the entire population

Question 3

Develop a good ____ before sample size calculations

Answer 3

Research hypothesis. A simple hypothesis contains one predictor and one outcome variable.

Question 4

Null hypothesis

Answer 4

No difference between groups. Proving the alternative hypothesis is not the goal.

Question 5

reject the null hypothesis

Answer 5

Means that you reject the negative, results in a positive.

Reject that there is not significant difference. Meaning that there is a significant difference.

Question 6

Analytic study sample size estimation (4)

Answer 6

1. State null and alternative hypothesis. One or two sided?
2. Select a statistical test based on predictor and outcome variables. Use Standard dev.
   Ex: Chi square, T test, correlation coefficient.
3. Estimate effect size. Difference between the two groups in your comparison that is meaningful.
4. Specify alpha (Type I error) or beta (type 2 error). Amount of error you are willing to accept.

Question 7

Type I error (alpha). Standard accepted amount?

Answer 7

Probability of a false positive.

a= 0.05 or 5%

Question 8

Type II error (beta). Standard accepted amount?

Answer 8

Probability of false negative.
b= 0.10-0.20
Power = 1-b
Power usually = 80-90%

Question 9

How to find your standard effect size

Answer 9

Significant difference/ Standard deviation

Question 10

Descriptive study sample size estimation (3)

Answer 10

Estimate proportion with dichotomous outcome or standard deviation of continuous outcome

Specify CI

Specify confidence level (95%)

Question 11

Sample size and power common errors

Answer 11

Sample size estimated too late in process.

Misinterpreting dichotomous variables.

Question 12

Dichotomous generally results in a ____ sample size than continuous variables

Answer 12

larger.

Question 13

Most effective way to change prescribing habits of a clinician

Answer 13

Direct to healthcare provider advertising. Drug rep travels to dr offices.

Question 14

Direct to consumer advertisting

Answer 14

Push and pull method. Push retail displays and pull people into drs offices to ask about drug.
FDA regulated.

Question 15

What happened in 1997 when FDA relaxed regulations about marketing

Answer 15

Significant increase in direct to consumer advertising and prescribing rate of drugs. Since, things have been further relaxed. Primary argument is to allow consumers to be more involved in healthcare.

Question 16

Academic Detailing

Answer 16

Good. Goal is to improve patient care and affect prescribing.

Academic detailers have no link to pharmaceutical industry. Independent.

Occurs in academic or non-commerical institutions. Education of prescribers by trained clinicians on EBM/RCTs.

Good in between of academia and drug industries coming to us.

Question 17

Sunshine act

Answer 17

Transparency. Minimize bribery by drug industries.

Question 18

How can you apply population EBM data to individual patient care?

Answer 18

1. Identify for the individual patient the objective of treatment.
   - Cure, prevention or recurrence, reassurance, relief.
2. Select most appropriate treatment
3. Specify treat goals and endpoints.
4. Discuss benefits vs risks/alternatives/costs

Question 19

CONSORT statement evaluates what kind of study

Answer 19

RCT

Question 20

Surrogate endpoints

Answer 20

A variable that is relatively easily measured and predicts are rare of distant outcome of therapeutic intervention.

Itself is not a direct measure of either harm or clinical benefit.

Biomarker intended to substitute for a clinical endpoint.

Question 21

Why would you use a surrogate endpoint?

Answer 21

Reduce cost, allow assessment of treatment whose primary outcomes are invasive or unethical.

Question 22

Downside of surrogate endpoints

Answer 22

May not be a true indicator of success rate of treamtment Indirect.
Represents only a single measure.
May come from animal studies.

Question 23

Examples of surrogate endpoints

Answer 23

Pharmacokinetics.
In vitro measures. 
Macroscopic appearance of tissues. 
Changes in levels of biological markers
Radiological appearance

Question 24

Pros and cons of animal studies

Answer 24

Pros:

1. Homogenous and inbred populations reduce cofounding variables.
2. Can evaluate multiple generations
3. Animals kept in strictly controlled environments.

Cons:

1. May not reflect same process in humans.
2. May need higher doses.
3. we are more diverse

Question 25

Features of ideal surrogate endpoint

Answer 25

1. Dose-reponse effect. Reliable, reproducible relationship with dose and response.
2. True predictor or disease.
3. Sensitive. Positive predictive value. (its good to be sensitive)
4. Specific. Negative predictive value (specific= nit picky. negative)

^so precise cut off between normal and abnormal.

Question 26

Dry eye and MMP-9

Answer 26

Surrogate endpoint for dry eye. Evaluates for dry eye by inflammation.

Question 27

Example of anecdotal evidence you should ignore when working with drug reps

Answer 27

Ignore “famous” optometrists using the product.

Question 28

STEP questions when working with drug reps

Answer 28

Safety 
Tolerability 
Efficacy 
Price 
and apply CONSORT checklist for reporting results.

Question 29

Two types of endpoints to a clinical trial study

Answer 29

Clinical (true) endpoint
Surrogate endpoint

The manipulation of surrogate endpoints by manufactures to cast their products in the most favorable light in their sales literature was the focus.

Question 30

Clinical endpoint

Answer 30

A characteristic or variable that reflects how a patient feels, functions, survives.