5/23/2016

1

Tracy Walker, RN, BSN, CCRP

Research NurseOHSU Knight Cancer Institute

503-346-1183walkertr@ohsu.edu

Exercise Questions to Keep in Mind

• Is there an adverse event?

• What is the severity?

• What is the relationship to study drug?

• Is it a serious adverse event?

• Is it an unanticipated problem?

• Does it need to be reported?

• To whom do you report?

• Is there a subject injury?

INJURY DEFINITION

• Subject injuries are adverse reactions: Arising directly from or contributed to by the research (MUST BE RELATED TO THE RESEARCH DRUG ITSELF OR A PROCEDURE REQUIRED BY THE PROTOCOL)

• Are not due to the subject’s primary disease or other condition

• Would not have been expected from the standard treatment using currently approved therapies for the subject’s condition– Determination of standard treatment is to be made by the PI using

generally recognized treatment options for your particular disease

5/23/2016

2

YES OR NO: SUBJECT INJURY?

• Disease progression?

NO

• Side effect of research medication the same as standard of care (SOC) side effect?

NO

• Anticipated side effect of research medication different than expected SOC side effect?

YES

• Unanticipated side effect of research medication differentthan expected SOC side effect?

YES

5/23/2016

COMPARING SIDE EFFECTS OF TREATMENTS FOR WRIST PAIN

• Usual treatment: Ibuprofen

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Dyspepsia

• Fatigue

• Increased bleeding risk

• Anxiety

Common side effects:

Study medication

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Diarrhea

• Rash

• Low K+

• Increased QTc

• Headaches

Unanticipated Problems – Remember: ‘Must fit all’

1. On Protocol

2. SAE

3. Unanticipated

4. Related or Possibly Related

Category 1

1. On Protocol

2. Anticipated AE or SAE

3. Related or Possibly Related

4. Occurring at a higher frequency or severity

Category 2

1. Unanticipated AE or SAE

2. Related or Possibly Related

3. May alter the risks and therefore warrants changes to the protocol, DSMP, or consent process

Category 3

1. Unanticipated

2. ‘Other’ events

3. May place subjects or others at greater risk of harm or discomfort. Harm need not have occurred.

Category 4

If event does not fit, it is not reportable.

5/23/2016

3

A Phase II Trial of the Safety and Efficacy of Abc -001 for the Treatment of Texting Induced Wrist Pain

2 yr trial Abc-001 50 mg tablet daily PO

30 subjectsAge > 18 years

Diagnosis: Wrist Pain

Adverse Events Reporting Exercise

History for Subject 507

• 41 year old female otherwise in good general health

• Diagnosis of wrist pain

• Medical hx: asthma, allergies

• Complains of intermittent, mild headaches

• No known drug allergies

• Meds: Zyrtec, multi-vitamin, ibuprofen

Physical for Subject 507

• Alert, oriented, NAD

• Normal physical exam

• BP 110/70, HR 76

5/23/2016

4

Progress Note

1/3/10 Subject 507 in for study visit. Reports feeling her

usual self. Takes study drug regularly. No side effects reported. No change in concomitant medications.

Subject Diary

1/10/10 Anxiety attack had to miss work. Felt nervous

all day.

1/12/10 Feeling better.

Back at work.

5/23/2016

Investigator’s Drug Brochure: Abc-001

Serious reactions

• Death

• Respiratory distress

• Severe neutropenia

• Hepatitis

• Excessive bleeding

Common side effects

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

• Abnormal LFT’s

• Rash

• Low K+

• Increased QTc

• Headaches

5/23/2016

5

Unanticipated Problems – Remember: ‘Must fit all’

1. On Protocol

2. SAE

3. Unanticipated

4. Related or Possibly Related

Category 1

1. On Protocol

2. Anticipated AE or SAE

3. Related or Possibly Related

4. Occurring at a higher frequency or severity

Category 2

1. Unanticipated AE or SAE

2. Related or Possibly Related

3. May alter the risks and therefore warrants changes to the protocol, DSMP, or consent process

Category 3

1. Unanticipated

2. ‘Other’ events

3. May place subjects or others at greater risk of harm or discomfort. Harm need not have occurred.

Category 4

If event does not fit, it is not reportable.

5/23/2016

COMPARING SIDE EFFECTS OF TREATMENTS FOR WRIST PAIN

• Usual treatment: Ibuprofen

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Dyspepsia

• Fatigue

• Increased bleeding risk

• Anxiety

Common side effects:

Study medication

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Diarrhea

• Rash

• Low K+

• Increased QTc

• Headaches

Progress Note

1/22/10 Subject 507 in for study visit. Reports nausea

lasting 2 hours on 1/18/10.

5/23/2016

6

5/23/2016

Investigator’s Drug Brochure: Abc-001

Serious reactions

• Death

• Respiratory distress

• Severe neutropenia

• Hepatitis

• Excessive bleeding

Common side effects

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

• Abnormal LFT’s

• Rash

• Low K+

• Increased QTc

• Headaches

Unanticipated Problems – Remember: ‘Must fit all’

1. On Protocol

2. SAE

3. Unanticipated

4. Related or Possibly Related

Category 1

1. On Protocol

2. Anticipated AE or SAE

3. Related or Possibly Related

4. Occurring at a higher frequency or severity

Category 2

1. Unanticipated AE or SAE

2. Related or Possibly Related

3. May alter the risks and therefore warrants changes to the protocol, DSMP, or consent process

Category 3

1. Unanticipated

2. ‘Other’ events

3. May place subjects or others at greater risk of harm or discomfort. Harm need not have occurred.

Category 4

If event does not fit, it is not reportable.

5/23/2016

COMPARING SIDE EFFECTS OF TREATMENTS FOR WRIST PAIN

• Usual treatment: Ibuprofen

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Dyspepsia

• Fatigue

• Increased bleeding risk

Common side effects:

Study medication

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Diarrhea

• Rash

• Low K+

• Increased QTc

• Headaches

5/23/2016

7

1/27/10 Reports fractured ankle from falling off a horse.

Outpatient surgical repair with excessive bleeding that

required overnight hospitalization. Study drug held for 2

weeks. Vicodin added to concomitant medications.

Progress Note

5/23/2016

Investigator’s Drug Brochure: Abc-001

Serious reactions

• Death

• Respiratory distress

• Severe neutropenia

• Hepatitis

• Excessive bleeding

Common side effects

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

• Abnormal LFT’s

• Rash

• Low K+

• Increased QTc

• Headaches

Unanticipated Problems – Remember: ‘Must fit all’

1. On Protocol

2. SAE

3. Unanticipated

4. Related or Possibly Related

Category 1

1. On Protocol

2. Anticipated AE or SAE

3. Related or Possibly Related

4. Occurring at a higher frequency or severity

Category 2

1. Unanticipated AE or SAE

2. Related or Possibly Related

3. May alter the risks and therefore warrants changes to the protocol, DSMP, or consent process

Category 3

1. Unanticipated

2. ‘Other’ events

3. May place subjects or others at greater risk of harm or discomfort. Harm need not have occurred.

Category 4

If event does not fit, it is not reportable.

5/23/2016

8

5/23/2016

COMPARING SIDE EFFECTS OF TREATMENTS FOR WRIST PAIN

• Usual treatment: Ibuprofen

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Dyspepsia

• Fatigue

• Increased bleeding risk

• Anxiety

Common side effects:

Study medication

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Diarrhea

• Rash

• Low K+

• Increased QTc

• Headaches

Progress Note

2/2/10 Subject 507 in for study visit. Reports recovering

from ankle fracture. Complains of increased headaches. Doubled her use of ibuprofen, continues pain medication and no change in other meds. Headaches are so severe, subject could not go to work.

Vital signs: BP 170/95, HR 90

5/23/2016

Investigator’s Drug Brochure: Abc-001

Serious reactions

• Death

• Respiratory distress

• Severe neutropenia

• Hepatitis

• Excessive bleeding

Common side effects

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

• Abnormal LFT’s

• Rash

• Low K+

• Increased QTc

• Headaches

5/23/2016

9

Unanticipated Problems – Remember: ‘Must fit all’

1. On Protocol

2. SAE

3. Unanticipated

4. Related or Possibly Related

Category 1

1. On Protocol

2. Anticipated AE or SAE

3. Related or Possibly Related

4. Occurring at a higher frequency or severity

Category 2

1. Unanticipated AE or SAE

2. Related or Possibly Related

3. May alter the risks and therefore warrants changes to the protocol, DSMP, or consent process

Category 3

1. Unanticipated

2. ‘Other’ events

3. May place subjects or others at greater risk of harm or discomfort. Harm need not have occurred.

Category 4

If event does not fit, it is not reportable.

5/23/2016

COMPARING SIDE EFFECTS OF TREATMENTS FOR WRIST PAIN

• Usual treatment: Ibuprofen

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Dyspepsia

• Fatigue

• Increased bleeding risk

• Anxiety

Common side effects:

Study medication

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Diarrhea

• Rash

• Low K+

• Increased QTc

• Headaches

Progress Note

2/15/10 Subject 507 in for study visit. Reports coldsymptoms of runny nose and non-productive cough. Tookcold remedies for 2 days. Does not recall the medicationnames, doses or dates taken.

Plan: Review the importance of keeping track of dates andany concomitant medications while participating in a study.

5/23/2016

10

5/23/2016

Investigator’s Drug Brochure: Abc-001

Serious reactions

• Death

• Respiratory distress

• Severe neutropenia

• Hepatitis

• Excessive bleeding

Common side effects

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

• Abnormal LFT’s

• Rash

• Low K+

• Increased QTc

• Headaches

Unanticipated Problems – Remember: ‘Must fit all’

1. On Protocol

2. SAE

3. Unanticipated

4. Related or Possibly Related

Category 1

1. On Protocol

2. Anticipated AE or SAE

3. Related or Possibly Related

4. Occurring at a higher frequency or severity

Category 2

1. Unanticipated AE or SAE

2. Related or Possibly Related

3. May alter the risks and therefore warrants changes to the protocol, DSMP, or consent process

Category 3

1. Unanticipated

2. ‘Other’ events

3. May place subjects or others at greater risk of harm or discomfort. Harm need not have occurred.

Category 4

If event does not fit, it is not reportable.

5/23/2016

COMPARING SIDE EFFECTS OF TREATMENTS FOR WRIST PAIN

• Usual treatment: Ibuprofen

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Dyspepsia

• Fatigue

• Increased bleeding risk

• Anxiety

Common side effects:

Study medication

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Diarrhea

• Rash

• Low K+

• Increased QTc

• Headaches

5/23/2016

11

• 2/20/10 Someone broke into your car and stole a few items … including the laptop on which you keep data for this study.

Progress Note

Unanticipated Problems – Remember: ‘Must fit all’

1. On Protocol

2. SAE

3. Unanticipated

4. Related or Possibly Related

Category 1

1. On Protocol

2. Anticipated AE or SAE

3. Related or Possibly Related

4. Occurring at a higher frequency or severity

Category 2

1. Unanticipated AE or SAE

2. Related or Possibly Related

3. May alter the risks and therefore warrants changes to the protocol, DSMP, or consent process

Category 3

1. Unanticipated

2. ‘Other’ events

3. May place subjects or others at greater risk of harm or discomfort. Harm need not have occurred.

Category 4

If event does not fit, it is not reportable.

Progress Note

3/3/10 Subject 507 in for study visit. Reports stomach ache about 30 minutes after taking study drug. Lasts 1 hour, does not require medication or interfere with her usual activity.

5/23/2016

12

Progress Note

3/15/10 Subject 507 in for study visit. Reports rapid

onset of intermittent blurred vision beginning 3/9/10

and lasting 3 days. Reports no other problems.

Continues study drug and no change in concomitant

medications.

5/23/2016

Investigator’s Drug Brochure : Abc-001

Serious reactions

• Death

• Respiratory distress

• Severe neutropenia

• Hepatitis

• Excessive bleeding

Common side effects

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

• Abnormal LFT’s

• Rash

• Low K+

• Increased QTc

• Headaches

Unanticipated Problems – Remember: ‘Must fit all’

1. On Protocol

2. SAE

3. Unanticipated

4. Related or Possibly Related

Category 1

1. On Protocol

2. Anticipated AE or SAE

3. Related or Possibly Related

4. Occurring at a higher frequency or severity

Category 2

1. Unanticipated AE or SAE

2. Related or Possibly Related

3. May alter the risks and therefore warrants changes to the protocol, DSMP, or consent process

Category 3

1. Unanticipated

2. ‘Other’ events

3. May place subjects or others at greater risk of harm or discomfort. Harm need not have occurred.

Category 4

If event does not fit, it is not reportable.

5/23/2016

13

5/23/2016

COMPARING SIDE EFFECTS OF TREATMENTS FOR WRIST PAIN

• Usual treatment: Ibuprofen

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Dyspepsia

• Fatigue

• Increased bleeding risk

• Anxiety

Common side effects:

Study medication

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Diarrhea

• Rash

• Low K+

• Increased QTc

• Headaches

Progress Note

4/15/10 Subject reports having horrible nightmares. According to her spouse, she is sleep walking and has become a danger to herself.

Subject is admitted to the sleep unit for overnight observation.

5/23/2016

Investigator’s Drug Brochure: Abc-001

Serious reactions

• Death

• Respiratory distress

• Severe neutropenia

• Hepatitis

• Excessive bleeding

Common side effects

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

• Abnormal LFT’s

• Rash

• Low K+

• Increased QTc

• Headaches

5/23/2016

14

Unanticipated Problems – Remember: ‘Must fit all’

1. On Protocol

2. SAE

3. Unanticipated

4. Related or Possibly Related

Category 1

1. On Protocol

2. Anticipated AE or SAE

3. Related or Possibly Related

4. Occurring at a higher frequency or severity

Category 2

1. Unanticipated AE or SAE

2. Related or Possibly Related

3. May alter the risks and therefore warrants changes to the protocol, DSMP, or consent process

Category 3

1. Unanticipated

2. ‘Other’ events

3. May place subjects or others at greater risk of harm or discomfort. Harm need not have occurred.

Category 4

If event does not fit, it is not reportable.

5/23/2016

COMPARING SIDE EFFECTS OF TREATMENTS FOR WRIST PAIN

• Usual treatment: Ibuprofen

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Dyspepsia

• Fatigue

• Increased bleeding risk

• Anxiety

Common side effects:

Study medication

• Nausea

• Vomiting

• Abdominal pain

• Abnormal LFT’s

• Diarrhea

• Rash

• Low K+

• Increased QTc

• Headaches

Exercise Questions

• Is there an adverse event?

• What is the severity?

• What is the relationship to study drug?

• Is it a serious adverse event?

• Is it an unanticipated problem?

• Does it need to be reported?

• To whom do you report?

• Is there a subject injury?

5/23/2016

15

Questions? Comments?