Lecture 4: Case Study: NAION

Question 1

Background

Answer 1

Drug class (PDE5 inhibitor) is taken on an as-needed basis for the treatment of erectile dysfunction. When study was initiated, there were only 3 PDE5 inhibitors on the market
NAION is a rare visual disorder presenting as a sudden partial loss of vision in one eye (incidence: 2.5 - 11.8 per 100,000 men aged 50+)
Post approval: cases of NAION seen in men using PDE5 inhibitors
NAION and ED share several risk factors including diabetes, hyperlipidemia and smoking

Question 2

Research Question

Answer 2

To determine whether recent exposure to PDE5 inhibitors is associated with onset of NAION (acute effect or class effect)

Question 3

What information is needed?

Answer 3

1) Risk of NAION in ppl exposed to PDE5i

2) Risk of NAION in people exposed to PDE5i if they had not been exposed (use risk of NAIONi in ppl unexposed)

Question 4

Case crossover design advantages

Answer 4

controls for confounding effects that were a concern, avoids potential biases associated with control selection since cases serve as their own controls
compare exposure and outcome with OR

Question 5

Case Crossover design (Case window)

Answer 5

time interval just prior to disease onset (exposed)

Question 6

Case Crossover design (Control window)

Answer 6

time period prior to case window divided into discrete independent intervals (unexposed)

Question 7

NAION Study strategy

Answer 7

Data source: Primary data required because secondary data not feasible
Study Design: Case crossover used because cohort design not feasible (rare endpoint, expensive) and case control leaves you with too much confounding

Question 8

Study Population

Answer 8

potential cases enrolled by 100+ ophthalmologists in US and Europe 2008-2012 (enrolled solely based on ophthalmologic criteria and irrespective of PDE5i exposure status

Question 9

Measurement of Outcome (NAION)

Answer 9

1) Cases were adjudicated by expert committee with extensive experience in NAION diagnosis (cases classified as Definite, possible, or non-NAION)
2) PDE5i exposure status was also masked from committee

Question 10

Measurement of Exposure (PDE5i)

Answer 10

PDE5i taken as needed for treatment of ED and must b obtained by subject self-report, so they needed STANDARDIZED approach to maximize accuracy
In the end PDE5i use obtained via telephone interview call center

Question 11

Phone Interview Questions

Answer 11

1) Participants were asked to recall dates of use during 2 months prior to NAION onset
2) They were asked about their prior use of several types of medications to avoid recall bias due to knowledge of research question.
3) Accuracy of recall improved via calendars, questions about average use and timing of significant life events (birthdays, trips)

Question 12

Results

Answer 12

Primary analysis: 43 definite NAION cases (1247 controls, OR = 2.15)
Sensitivity analysis: 64 definite and possible NAION cases (1856 controls and OR = 2.36)

Question 13

Conclusion

Answer 13

1) Results indicate a 2-fold increased risk of NAION associated with recent use of PDE5i
2) Bias from inaccurate recall was unlikely to have substantially affected results
3) Weekly use of PDE5 inhibitors estimated to add 3 NAION cases per 100,000 men aged 50+ years each year