drug lit - exam 1 RCT 2

Question 1

patient case

Answer 1

During your community pharmacy IPPE rotation, Mrs. J, a 32-year-old pregnant woman approaches the counter to pick up a refill for her labetalol.

Mrs. J tells you that since she last came to the pharmacy, she has been reading about labetalol use in pregnancy.

She read that treating hypertension in pregnancy can cause the baby to be small and doesn’t really help the mom either.

She’s wondering if she should continue to take labetalol.

Question 2

Hypertensive Disorders in pregnancy

Answer 2

Most common medical condition complicating pregnancy

Hypertensive disorders
- New onset hypertension
- Develops ≥ 20 week gestation
Chronic hypertension
- Diagnosed prior to pregnancy or before 20 weeksgestation
- Preeclampsia

Systolic (SBP)
- ≥ 140 mm Hg

Diastolic (DBP)
- ≥ 90 mm Hg

Question 3

Complications of hypertension in Pregnancy

Answer 3

Maternal Outcomes:
- Preeclampsia/eclampsia
Maternal death
Stroke
Heart failure
Pulmonary edema
Acute kidney injury

Fetal Outcomes
- Placental abruption
- Small for gestational age
- Perinatal death

Question 4

Chronic Hypertension Treatment

Answer 4

American College of Obstetricians and Gynecologists (ACOG) recommendations:
Antihypertensive therapy for women with:
- Persistent chronic hypertension with SBP ≥ 160 mm Hg or DBP ≥ 105 mm Hg(ACOG Level B)

• Gestational hypertension or preeclampsia with severe hypertension(sustained SBP ≥ 160 mm Hg or DBP ≥ 110 mm Hg) (ACOG Level B)

ACOG Level B
- “Based on limited or inconsistent scientific evidence”

Options:
- Labetalol 200-2400 mg/day PO in 2-3 divided doses
- Nifedipine ER 30-120 mg PO daily
- Methyldopa 0.5-3 g/day PO in 2-4 divided doses

Question 5

What do we know and not know?

Answer 5

Antihypertensives for chronic hypertension or nonsevere hypertension during pregnancy:
- May reduce frequency of severe hypertension (BP ≥160/110 mm Hg)
- Effects on maternal and neonatal outcomes are uncertain
- Atenolol may increase small-for-gestational-age (SGA)

Question 6

The Abstract

Answer 6

Give it a “quick” read

Is the rest of the article worth reading?
- What it the population?
- What is the intervention?
- What is the comparator?
- What is the outcome?

Question 7

Our study

Answer 7

New England Journal of Medicine

Affiliated with Massachusetts Medical Society
- Strength

Peer-reviewed - Strength

Impact factor = 176.1
- Strength

Question 8

for the HTN in pregnant women

Answer 8

Appraisal Questions
Background
- Did the authors provide sufficient background information to demonstrate the rationale for the study?
- How will this trial add to the existing knowledge?
- Will the results of this trial be meaningful to practice?
- What is the objective of this study? Does it include all elements of the PICO question?

Question 9

What is the objective of the study?

P
I
C
O

Answer 9

P = pregnant women with mild to chronic HTN

I = antihypertensive medications to target BP < 140/90

C = no treatment; with hold antihypertensives until BP > 160/105

O = maternal

in pregnant women with mild HTN will adminstering antihypertensives with a BP goal of <140/90 improve maternal health

Question 10

What is the null hypothesis of this study?

A
Administering antihypertensives to pregnant women with mild hypertension will have worse maternal and perinatal outcomes compared to withholding antihypertensives until the BP is ≥ 160/105.

B
Administering antihypertensives to pregnant women with mild hypertension will have no impact on maternal and perinatal outcomes compared to withholding antihypertensives until the BP is ≥ 160/105.

C
Administering antihypertensives to pregnant women with mild hypertension will improve maternal and perinatal outcomes compared to withholding antihypertensives until the BP is ≥ 160/105.

Answer 10

B
Administering antihypertensives to pregnant women with mild hypertension will have no impact on maternal and perinatal outcomes compared to withholding antihypertensives until the BP is ≥ 160/105.

null hypothesis ties into type I error

Question 11

What is the alternative hypothesis of this study?

A
Administering antihypertensives to pregnant women with mild hypertension will have worse maternal and perinatal outcomes compared to withholding antihypertensives until the BP is ≥ 160/105.

B
Administering antihypertensives to pregnant women with mild hypertension will have no impact on maternal and perinatal outcomes compared to withholding antihypertensives until the BP is ≥ 160/105.

C
Administering antihypertensives to pregnant women with mild hypertension will improve maternal and perinatal outcomes compared to withholding antihypertensives until the BP is ≥ 160/105.

Answer 11

C
Administering antihypertensives to pregnant women with mild hypertension will improve maternal and perinatal outcomes compared to withholding antihypertensives until the BP is ≥ 160/105.

Question 12

Appraisal Questions

Answer 12

Study Design
Was an appropriate study design used to answer the question? - mostly always yes :)

What type of blinding was used? Was this type appropriate?

Was randomization included? If so, what type was used? Was this appropriate?

Was allocation concealed? If so, what was the method of allocationconcealment?

How strong is this type of study in terms of the hierarchy of EBM?

Funding
If a biopharmaceutical company sponsor was heavily involved in study design, data monitoring and analysis, and manuscript preparation, how might this introduce bias to the study?

Enrollment
Where did the patients come from? Was a selection bias present?
Was subject recruitment described? If so, how were subjects recruited? Was the method appropriate?

pragmatic means real world

Question 13

This trial was Prospective

A
True

B
False

C
Unsure

Answer 13

A
True

Question 14

This trial was Multi-centered

A
True

B
False

C
Unsure

Answer 14

A
True
more than 1 site - this is a strength

relates to external validity (ability to apply to people so the more sites we have the more diverse it will be) by increasing it

Question 15

This trial was Double Blind

A
True

B
False

C
Unsure

Answer 15

B
False
because it was open-label
this is a weakness and that it is the biggest weakness in this study

Question 16

What type of randomization was used?

A
Simple

B
Blocked

C
Stratified

Answer 16

blocked & Stratified
we use stratified to evenly distribute confounding factors so they stratified based on site - so this is a strength

Question 17

Allocation was concealed - the randomizer does not know what treatments are given. The randomization is not known

A
True

B
False

C
Unsure

Answer 17

A
True
they used a web-based system

Question 18

The study duration was appropriate

A
Yes

B
No

C
Maybe

Answer 18

B
No

Question 19

Which study is most likely to be biased by pharmaceutical industry funding?

A
A

B
B

C
C

Answer 19

C - It is sponsored by Eli Lilly

Question 20

Appraisal Questions

Answer 20

Inclusion/Exclusion Criteria
- Are inclusion and exclusion criteria pertinent and logical to the study design?
- Are they all‐inclusive?
- Are they biased?
- Do they limit the external validity of the study results?

Question 21

Which of the following patients could the results of this study not be generalized to? (Select All that apply)

A
A 40-year-old woman carrying twins

B
A 38-year-old woman with chronic hypertension prior to pregnancy

C
A 27-year-old woman with chronic kidney disease

D
A 22-year-old woman with a BP of 158/102

E
A 30-year-old woman diagnosed with diabetes at age 20 years

Answer 21

A
A 40-year-old woman carrying twins

C
A 27-year-old woman with chronic kidney disease

GREAT JOB MICHELLE YOU WILL GET AN A ON THIS EXAM IN JESUS NAME AMEN!!!!

Question 22

Appraisal Questions

Answer 22

Intervention/Comparator
- Are the interventions/methods logical?
- Is sufficient detail provided?
- Are the intervention/comparator consistent with current practice?
- Is the product available in the US?
- Which ancillary treatments were permitted? Could they have affected the outcome?

Question 24

Which one of the following statements is true?

A
The intervention was titrated which limits internal validity.

B
The intervention used is consistent with practice in the US.

C
The trial included a run-in phase which will lead to selection bias. - RUN-IN Phase is when they are treated before the study

D
The trial used ancillary treatments which will lead to confounding.

Answer 24

B
The intervention used is consistent with practice in the US.

Question 25

Appraisal Questions

Answer 25

Monitoring:
Is this consistent/feasible in clinical practice?
Are there differences in management between the groups being studied?
Are the monitoring parameters objective or subjective?
Was adherence measured?

Question 26

There were no differences in how the two groups were followed.

A
True

B
False

C
Unsure

Answer 26

false
- followed according to the usual practice at the sites and because they are at different sites they may be different between the sites

Question 27

Appraisal Questions

Answer 27

Endpoints
Are the endpoints patient-oriented that matter (POEM) or disease-oriented?

Are the endpoints appropriate for the question being asked?

Are the endpoints something typically measured in clinical practice?

Were any instruments used previously validated?

Are the outcomes/endpoints objective?

Were the outcomes independently adjudicated (verified) by a third party?

Question 28

The primary endpoint is … (select all that Apply)

A
Patient-oriented evidence

B
Disease oriented evidence

C
A composite endpoint

D
A surrogate marker

Answer 28

A
Patient-oriented evidence

C
A composite endpoint - good job!!!! you will get an A on this exam in Jesus’ name amen

Question 29

The primary outcome was or was not independently adjudicated by a third party blinded to treatment allocation.

true

false

Answer 29

true - it was!

Question 30

the endpoints are something typically measured in clinical practice.

A
True

B
False

C
Unsure

Answer 30

A
True

Question 31

Appraisal Questions

Answer 31

Statistics

Were the alpha (α) and beta (β) values appropriate?
alpha was 0.05

Was the necessary sample size calculated?

Was intention-to-treat and/or per-protocol analysis used?

Was the type of data analysis used appropriate for the clinical question?

What can you conclude if the analysis was post hoc versus a priori?

Question 32

What was the Alpha in this study?

Answer 32

0.05

Question 33

beta
the power is 85%

Answer 33

power = 1 - beta

0.85 = 1 - beta

0.15

correct!

Question 34

what effects power in a study

Answer 34

sample size

event rate

Question 35

Which one of the following statements is True?

A
The study comparisons were chosen a priori which is a weakness

B
The study comparisons were chosen post hoc which is a weakness

C
This study used a per-protocol analysis which is a strength

D
This study used an intention-to-treat analysis which is a strength

Answer 35

D
This study used an intention-to-treat analysis which is a strength - found on the first sentence!

Question 36

Our study

Answer 36

What is the purpose of the per-protocol analysis? - because we want to see a sensitivity analysis

When multiple analyses are performed, the risk of a type I error increases
- Lower alpha to account for this

Question 37

Which one of the following statistical tests should be used for the primary composite endpoint analysis?

A
Unpaired student t-test

B
Kruskal-Wallis test

C
Chi-square test

D
ANOVA

Answer 37

C
Chi-square test
2 groups and this is discrete and categorical data because they have not met the composite endpoint or not

This will be on the midterm

Question 38

Appraisal Questions

Answer 38

Patients
Were the subject demographics between groups similar at baseline? If not, were the differences likely to have an effect on the outcome data?

Were at least 80% of study participants included in the data analysis?

Did the authors describe what happened to dropouts? Were the patients lost to follow-up consistent between the groups?

Is the population generalizable to the typical population with this condition?

Question 39

Endpoints

Answer 39

Was the endpoint found to be statistically significant? If not, was the study adequately powered to detect a difference in this outcome?

Are the results clinically significant? Calculate the ARR, RRR, etc. Interpret the RR, HR, etc. Is the magnitude of the results great enough to have a clinically significant effect (meaningful to patients and providers)?

Calculate NNT/NNH for all relevant endpoints that are dichotomous and statistically significant.

Critique the confidence interval, if available.

Question 40

The results of the primary composite outcome are statistically significant.

A
True

B
False

C
Unsure

Answer 40

A
True
can look at the p-value (has to be less than 0.05)
can look at the CI (cannot include 1 if a discrete endpoint)

Question 41

Which of the following results are statistically significant? (Select ALL that Apply)

A
Preeclampsia with severe features: Adjusted RR 0.82; 95% CI 0.70-0.92

B
Medically indicated preterm birth at < 35 weeks: Adjusted RR 0.73; 95% CI 0.60-0.89

C
Placental abruption: Adjusted RR 0.88; 95% CI 0.49-1.59

D
Fetal or neonatal death at < 28 days: Adjusted RR 0.81; 95% CI 0.54-1.22

Answer 41

A
Preeclampsia with severe features: Adjusted RR 0.82; 95% CI 0.70-0.92

B
Medically indicated preterm birth at < 35 weeks: Adjusted RR 0.73; 95% CI 0.60-0.89

Question 42

Describe the result of the primary composite endpoint

Interpret the adjusted RR

Interpret the NNT

Answer 42

RRR = 1 - 0.82 = 0.18

ARR = 6.8%

NNT = 100/6.8 = 14.7 round up to 15

Interpret the adjusted RR
- the risk of the primary composite endpoint was reduced by 18% in the active treatment group compared to the control group

Interpret the NNT
- 15 patients need to be treated with antihypertensives compared to withholding treatments for the duration of the pregnancy in order to prevent 1 composite primary outcome

Question 43

From Our Study

Answer 43

Primary composite outcome

Primary outcome components
Preeclampsia with severe features

Preterm birth before 35 weeks

Safety

Question 44

From Previous Data

Answer 44

Chronic hypertension affects 3-5% of pregnancies

Preeclampsia occurs in 17-25% of patients with chronic hypertension

Preterm birth occurs in 12-34% of patients with chronic hypertension
- Risk increases with higher blood pressure

Question 45

The results of the trial are clinically significant.

A
True

B
False

C
Unsure

Answer 45

A
True