1. Adverse Events for VOICE Additional Examples

2. Is it an Adverse Event? Suppose a participant is found to have a grade 3 ALT after her Month 1 visit. Is this an adverse event? Is it a reportable adverse event?

3. Is it an Adverse Event? Suppose a participant is found to have a grade 1 ALT after her Month 1 visit. Is this an adverse event?

4. Is it an Adverse Event? Suppose a participant is found to have a grade 1 ALT after her Month 1 visit. Her baseline labs at Screening Part 1 were normal. Is this an adverse event? Is it reportable?

5. Is it an Adverse Event? Suppose a participant is found to have a grade 1 ALT after her Month 1 visit. Her baseline labs at Screening Part 1 were normal. Per protocol, you repeat her lab tests one week later and her ALT is normal. She presents for Month 3 visit and you repeat ALT as per the protocol. Now her ALT is a grade 1. In this scenario. How many AEs have occurred?

6. Is it an Adverse Event? Suppose a participant is found to have a grade 1 ALT after her Month 1 visit. Her baseline labs at Screening Part 1 were normal. Per protocol, you repeat her lab tests one week later and her ALT is normal. She presents for Month 3 visit and you repeat ALT as per the protocol. Now her ALT is a grade 1. In this scenario. How many AEs have occurred? Are any reportable? Are any serious?

7. Is it an Adverse Event? Suppose a participant presents for her Month 5 visit and reports burning with urination and urinary frequency. You decide to do a urine dipstick in light of her symptoms suggestive of a urinary tract infection. The dipstick is positive for leukocyte esterase, negative for nitrite, positive for protein (1+) and negative for glucose. Has an AE occurred? If so, how many? Which, if any, are reportable? Are any serious?

8. Follow-Up Suppose a participant presents for her Month 5 visit and reports burning with urination and urinary frequency. You decide to do a urine dipstick in light of her symptoms suggestive of a urinary tract infection. The dipstick is positive for leukocyte esterase, negative for nitrite, positive for protein (1+) and negative for glucose. You elect to treat these symptoms with an antibiotic because your suspicion for a urinary tract infection is high. When will you have her come back to the clinic?

9. Is it an Adverse Event? Suppose a participant presents for her Month 5 visit and reports burning with urination and urinary frequency. You decide to do a urine dipstick in light of her symptoms suggestive of a urinary tract infection. The dipstick is positive for leukocyte esterase, positive for nitrite, positive for protein (1+) and negative for glucose. Has an AE occurred? If so, how many? Which, if any, are reportable? Are any serious?

10. Follow-Up Suppose a participant presents for her Month 5 visit and reports burning with urination and urinary frequency. You decide to do a urine dipstick in light of her symptoms suggestive of a urinary tract infection. The dipstick is positive for leukocyte esterase, positive for nitrite, positive for protein (1+) and negative for glucose. You elect to treat these symptoms with an antibiotic because your suspicion for a urinary tract infection is high. When will you have her come back to the clinic?

11. Follow-Up Suppose a participant presents for her Month 5 visit and reports burning with urination and urinary frequency. You decide to do a urine dipstick in light of her symptoms suggestive of a urinary tract infection. The dipstick is positive for leukocyte esterase, positive for nitrite, positive for protein (1+) and negative for glucose. You elect to treat these symptoms with an antibiotic because your suspicion for a urinary tract infection is high. You ask her to come in for a urine dipstick per protocol 10 days after the proteinuria was detected in the clinic. The dipstick is negative for proteinuria. What is the resolution date for the urinary tract infection adverse event?

12. Follow-Up Suppose a participant presents for her Month 5 visit and reports burning with urination and urinary frequency. You decide to do a urine dipstick in light of her symptoms suggestive of a urinary tract infection. The dipstick is positive for leukocyte esterase, positive for nitrite, positive for protein (1+) and negative for glucose. You elect to treat these symptoms with an antibiotic. You ask her to come in for a urine dipstick per protocol 10 days after the proteinuria was detected in the clinic. She has no complaints. You perform a dipstick and find that the proteinuria is still 1+. The participant completed treatment and has not other symptoms besides the 1+ protein result. Can you resolve the urinary tract infection AE now?

13. Is it an Adverse Event Suppose a participant presents for her month 6 visit and reports that she was admitted to the hospital 3 weeks prior after an argument with her husband escalated and he stabbed her in the neck. She was hospitalized for 1 week at which point she underwent exploratory surgery in her neck. Today she feels well and is noted to have a 5 cm scar on the right side of her neck. Has an AE occurred? How many? Which, if any, are reportable? Which, if any, are serious? Which, if any, are EAEs?

14. Is it an Adverse Event? Suppose a participant presents for her month 6 visit and reports that she was admitted to the hospital 3 weeks prior after an argument with her husband escalated and he stabbed her in the neck. She was hospitalized for 1 week at which point she underwent exploratory surgery in her neck. Today she feels well and is noted to have a 5 cm scar on the right side of her neck. Has a social harm occurred? Should it be reported?

15. Is it an Adverse Event? A woman presents for her enrollment visit and complains of a thick vaginal discharge and itch. You perform a pelvic exam and wet mount and diagnose the woman with a candida infection. Has an AE occurred?

16. Is it an Adverse Event A participant presents for her Month 12 visit and is found to have a positive pregnancy test. Has an AE occurred?

17. Is it an Adverse Event A participant presents for her Month 12 visit and is found to have a positive pregnancy test. She continues in the study off product and at her Month 18 visit, when she is 25 weeks pregnant, she reports an episode of vaginal bleeding. Has an AE occurred? What term would you use to describe it?

18. Is it an Adverse Event A participant presents for her Month 12 visit and is found to have a positive pregnancy test. She continues in the study off product and at her Month 18 visit, when she is 25 weeks pregnant, she reports an episode of vaginal bleeding and cramping. You refer her to the local hospital where she goes on to deliver later that day. Her baby was still born at delivery. In this scenario has an AE occurred? Is so, how many?

19. Is this an Adverse Event? A participant’s mother calls to notify the site that her daughter was hospitalized with dehydration secondary to nausea and vomiting yesterday. The mother relays to you that her daughter is receiving IVF but beyond that she does not know what the underlying diagnosis is or what other treatment the participant is receiving. Has an AE occurred? If so, how many?

20. Is this an SAE? A participant’s mother calls to notify the site that her daughter was hospitalized with dehydration secondary to nausea and vomiting yesterday. The mother relays to you that her daughter is receiving IVF but beyond that she does not know what the underlying diagnosis is or what other treatment the participant is receiving. Have any reportable AEs occurred? Are any serious?

21. Is this an EAE? A participant’s mother calls to notify the site that her daughter was hospitalized with dehydration secondary to nausea and vomiting yesterday. The mother relays to you that her daughter is receiving IVF but beyond that she does not know what the underlying diagnosis is or what other treatment the participant is receiving. Have any expedited AEs occurred? If so, when do the sites need to notify DAIDS?

22. Is this an Adverse Event? A participant presents to her Month 15 visit and reports a three day history of headache, fever, and abdominal pain. Has an AE occurred? If so, how many AEs? Are they reportable?

23. Is this an Adverse Event? A participant presents to her Month 15 visit and reports a three day history of headache, fever, and abdominal pain. After your assessment you grade the AEs as follows: Grade 1 fever, Grade 2 headache, Grade 2 abdominal pain. How many AEs are reportable?

24. Is this an Adverse Event? A participant presents to her Month 15 visit and reports a three day history of headache, fever, and abdominal pain. After your assessment you grade the AEs as follows: Grade 1 fever, Grade 2 headache, Grade 2 abdominal pain. You perform laboratory tests and find that she has a grade 1 AST, grade 2 ALT and a positive blood smear for malaria. How many AEs have occurred? Which are reportable?

25. Is this an Adverse Event? You learn that a participant was in a motor vehicle accident and suffered a broken arm and laceration on her head. She was evaluated in the casualty department but not admitted to the hospital. Have any AEs occurred? If so, how many? How many are reportable?

26. Is this an Adverse Event? You learn that a participant was in a motor vehicle accident and suffered a broken arm and laceration on her head. She was evaluated in the casualty department but not admitted to the hospital. She presents to the clinic three days after the accident with erythema and purulent discharge from her face laceration. In total, how many AEs have occurred? How many are reportable?

27. Is this an Adverse Event A participant presents for her Month 12 visit and is noted to have a small ulcer on her right labia. It is non tender and she was unaware of it. She is on oral product. Has an AE occurred? What if the participant complained about the lesion, would an AE have occurred in that situation?

28. Is this an Adverse event? A participant’s baseline creatinine is 0.4. (ULN=1.2). At her Month 9 visit she is found to have a creatinine of 0.7. Has an AE occurred?

29. Is this an Adverse Event? A participant presents to her Month 6 visit complaining of dysuria, frequency, and hematuria. Has an AE occurred?

30. Is this an Adverse Event? A participant presents to her Month 6 visit complaining of dysuria, frequency, and hematuria. You dip her urine and find +leukocytes, + blood, +nitrites, and 1+ proteinuria. Has an AE occurred? If so, how many? Are any reportable? Are any serious?

31. Is this an Adverse Event? A participant presents to her Month 6 visit complaining of dysuria, frequency, and hematuria. You dip her urine and find +leukocytes, + blood, +nitrates, and 1+ proteinuria. You prescribe an antibiotic and ask her to call the site if her symptoms do not resolve within 5 days. She presents to the clinic 3 days later with complaints of fever, chills, and back pain. You suspect pylenephritis and send her to the casualty department for evaluation. She is ultimately admitted to the hospital for two days of antibiotics. In this scenario, how many AEs have occurred? Are they serious?