Physicians were aware to varying degrees of the risks associated with retigabine. |
Subgroup analyses showed that both the physicians who read the retigabine education letter and those who had prescribed retigabine had better recall of information. |
To strengthen risk-minimization efforts for retigabine and following the identification of new emerging risks in 2013, GSK has since sent an updated ‘Dear Healthcare Professional’ letter and initiated another EU survey to assess how effectively specific risks associated with retigabine use are communicated. |
1 Introduction
2 Methods
2.1 Study Design
2.2 Setting
2.3 Subjects
2.4 Screening and Baseline Assessments
2.5 Statistical Analysis
2.6 Populations and Subgroup Analysis
3 Results
3.1 Study Population
3.2 Participants
3.3 Survey Results
Question | All eligible physicians, all seven countries (n = 294) | Physicians who prescribed RTG only (n = 144) | Physicians who read the RTG information letter (n = 189) | Physicians who did not read the RTG information letter (n = 105) | ||||
---|---|---|---|---|---|---|---|---|
n
| % (95 % CI) |
n
| % (95 % CI) |
n
| % (95 % CI) |
n
| % (95 % CI) | |
Question 6: For which of the following conditions is Trobalt™ approved for use? | ||||||||
Migraine | 2 | 0.7 | 0 | 0.0 | 1 | 0.5 | 1 | 1.0 |
Partial-onset seizuresa
| 269 | 91.5 (87.7–94.4) | 139 | 96.5 (92.1–98.9) | 178 | 94.2 (89.8–97.1) | 91 | 86.7 (78.6–92.5) |
All types of seizures | 11 | 3.7 | 5 | 3.5 | 7 | 3.7 | 4 | 3.8 |
All of the above | 3 | 1.0 | 0 | 0.0 | 2 | 1.1 | 1 | 1.0 |
None of the above | 3 | 1.0 | 0 | 0.0 | 1 | 0.5 | 2 | 1.9 |
I don’t know | 6 | 2.0 | 0 | 0.0 | 0 | 0.0 | 6 | 5.7 |
Question 7: Is Trobalt™ indicated for use as monotherapy? | ||||||||
Yes | 16 | 5.4 | 6 | 4.2 | 6 | 3.2 | 10 | 9.5 |
Noa
| 259 | 88.1 (83.8–91.6) | 136 | 94.4 (89.3–97.6) | 178 | 94.2 (89.8–97.1) | 81 | 77.1 (67.9–84.8) |
I don’t know | 19 | 6.5 | 2 | 1.4 | 5 | 2.6 | 14 | 13.3 |
Question 8: What is the maximum recommended daily maintenance dose of Trobalt™ for most patients?b
| ||||||||
600 mg | 16 | 5.5 | 12 | 8.4 | 12 | 6.4 | 4 | 3.8 |
900 mg | 28 | 9.6 | 20 | 14.0 | 19 | 10.1 | 9 | 8.6 |
1200 mga
| 200 | 68.3 (62.6–73.6) | 104 | 72.7 (64.7–79.8) | 146 | 77.7 (71.0–83.4) | 54 | 51.4 (41.5–61.3) |
2000 mg | 1 | 0.3 | 0 | 0.0 | 0 | 0.0 | 1 | 1.0 |
None of the above | 3 | 1.0 | 1 | 0.7 | 2 | 1.1 | 1 | 1.0 |
I don’t know | 45 | 15.4 | 6 | 4.2 | 9 | 4.8 | 36 | 34.3 |
Question 9: Which one of the following statements is true? (please select the best response) | ||||||||
Trobalt™ should be taken once a day | 16 | 5.4 | 4 | 2.8 | 7 | 3.7 | 9 | 8.6 |
Trobalt™ should be taken twice a day | 33 | 11.2 | 18 | 12.5 | 19 | 10.1 | 14 | 13.3 |
Trobalt™ should be taken three times a daya
| 218 | 74.1 (68.7–79.1) | 121 | 84.0 (77.0–89.6) | 161 | 85.2 (79.3–89.9) | 57 | 54.3 (44.3–64.0) |
Trobalt™ should be taken four times a day | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
None of the above | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
I don’t know | 27 | 9.2 | 1 | 0.7 | 2 | 1.1 | 25 | 23.8 |
Question 10: When increasing the dose, what is the maximum total daily dose at which Trobalt™ can be increased once every 7 days? (please select the best response) | ||||||||
50 mg | 30 | 10.2 | 9 | 6.3 | 17 | 9.0 | 13 | 12.4 |
150 mga
| 214 | 72.8 (67.3–77.8) | 114 | 79.2 (71.6–85.5) | 152 | 80.4 (74.0–85.8) | 62 | 59.0 (49.0–68.5) |
300 mg | 35 | 11.9 | 17 | 11.8 | 15 | 7.9 | 20 | 19.0 |
600 mg | 7 | 2.4 | 4 | 2.8 | 4 | 2.1 | 3 | 2.9 |
None of the above | 8 | 2.7 | 0 | 0.0 | 1 | 0.5 | 7 | 6.7 |
Question 11: Which of the following statements is true? (please select the best response) | ||||||||
There are no lower age limits for Trobalt™ usage | 10 | 3.4 | 3 | 2.1 | 5 | 2.6 | 5 | 4.8 |
The youngest age at which Trobalt™ can be used is 12 | 18 | 6.1 | 12 | 8.3 | 11 | 5.8 | 7 | 6.7 |
The youngest age at which Trobalt™ can be used is 18a
| 230 | 78.2 (73.1–82.8) | 120 | 83.3(76.2–89.0) | 165 | 87.3 (81.7–91.7) | 65 | 61.9 (51.9–71.2) |
I don’t know | 36 | 12.2 | 9 | 6.3 | 8 | 4.2 | 28 | 26.7 |
Question 12: The quickest time by which the minimum maintenance dose of 600 mg should be reached is the third week | ||||||||
Truea
| 197 | 67.0 (61.3–72.4) | 98 | 68.1 (59.8–75.6) | 141 | 74.6 (67.8–80.6) | 56 | 53.3 (43.3–63.1) |
False | 62 | 21.1 | 39 | 27.1 | 38 | 20.1 | 24 | 22.9 |
I don’t know | 35 | 11.9 | 7 | 4.9 | 10 | 5.3 | 25 | 23.8 |
Question 13: For the general population, the recommended total initial dosage should be 150 mg per day for 1 week | ||||||||
True | 89 | 30.3 | 49 | 34.0 | 62 | 32.8 | 27 | 25.7 |
Falsea
| 178 | 60.5 (54.7–66.2) | 93 | 64.6 (56.2–72.4) | 121 | 64.0 (56.7–70.9) | 57 | 54.3 (44.3–64.0) |
I don’t know | 27 | 9.2 | 2 | 1.4 | 6 | 3.2 | 21 | 20.0 |
Question 14: People taking Trobalt™ had a higher chance of experiencing which of the following risks in clinical studies (please select all that apply) | ||||||||
Urinary retentiona
| 190 | 64.6 (58.9–70.1) | 107 | 74.3 (66.4–81.2) | 140 | 74.1 (67.2–80.2) | 50 | 47.6 (37.8–57.6) |
Confusional statea
| 195 | 66.3 (60.6–71.7) | 102 | 70.8 (62.7–78.1) | 140 | 74.1 (67.2–80.2) | 55 | 52.4 (42.4–62.2) |
Hallucinationsa
| 164 | 55.8 (49.9–61.5) | 86 | 59.7 (51.2–67.8) | 116 | 61.4 (54.0–68.4) | 48 | 45.7 (36.0–55.7) |
Psychotic disordersa
| 159 | 54.1 (48.2–59.9) | 80 | 55.6 (47.1–63.8) | 112 | 59.3 (51.9–66.3) | 47 | 44.8 (35.0–54.8) |
Myocardial infarction | 8 | 2.7 | 2 | 1.4 | 5 | 2.6 | 3 | 2.9 |
Renal carcinoma | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
All of the above | 11 | 3.7 | 6 | 4.2 | 7 | 3.7 | 4 | 3.8 |
None of the above | 12 | 4.1 | 8 | 5.6 | 6 | 3.2 | 6 | 5.7 |
I don’t know | 37 | 12.6 | 3 | 2.1 | 7 | 3.7 | 30 | 28.6 |
Question 15: It is known from controlled studies that adverse events related to voiding dysfunction generally tend to be reported how soon after starting Trobalt™? | ||||||||
Within the first week | 32 | 10.9 | 16 | 11.1 | 16 | 8.5 | 16 | 15.2 |
Within the first 8 weeksa
| 162 | 55.1 (49.2–60.9) | 96 | 66.7 (58.3–74.3) | 127 | 67.2 (60.0–73.8) | 35 | 33.3 (24.4–43.2) |
After 4 months | 3 | 1.0 | 1 | 0.7 | 1 | 0.5 | 2 | 1.9 |
After 12 months | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
I don’t know | 97 | 33.0 | 31 | 21.5 | 45 | 23.8 | 52 | 49.5 |
Question 16: It is known from controlled studies that confusional state, hallucinations, and/or psychotic disorders generally tend to be reported how soon after starting Trobalt™? | ||||||||
4 weeks | 76 | 25.9 | 47 | 32.6 | 54 | 28.6 | 22 | 21.0 |
8 weeksa
| 117 | 39.8 (34.2–45.6) | 60 | 41.7 (33.5–50.2) | 92 | 48.7 (41.4–56.0) | 25 | 23.8 (16.0–33.1) |
12 weeks | 13 | 4.4 | 9 | 6.3 | 10 | 5.3 | 3 | 2.9 |
16 weeks | 2 | 0.7 | 0 | 0.0 | 0 | 0.0 | 2 | 1.9 |
I don’t know | 86 | 29.3 | 28 | 19.4 | 33 | 17.5 | 53 | 50.5 |
Question 17: Which of the following urinary symptoms, if any, should you specifically advise patients taking Trobalt™ to watch out for? (please select the best response) | ||||||||
Pain when urinating | 4 | 1.4 | 1 | 0.7 | 1 | 0.5 | 3 | 2.9 |
Difficulty starting urination | 51 | 17.3 | 22 | 15.3 | 33 | 17.5 | 18 | 17.1 |
Slow stream | 1 | 0.3 | 1 | 0.7 | 1 | 0.5 | 0 | 0.0 |
Inability to pass urine | 46 | 15.6 | 24 | 16.7 | 32 | 16.9 | 14 | 13.3 |
All of the abovea
| 163 | 55.4 (49.6–61.2) | 90 | 62.5 (54.1–70.4) | 118 | 62.4 (55.1–69.4) | 45 | 42.9 (33.2–52.9) |
None of the above | 1 | 0.3 | 0 | 0.0 | 0 | 0.0 | 1 | 1.0 |
I don’t know | 28 | 9.5 | 6 | 4.2 | 4 | 2.1 | 24 | 22.9 |
Question 18: According to the Trobalt™ Physician’s Guide, appropriate dose titrations may minimize the risk of which of the following adverse events? (please select the best response) | ||||||||
QT prolongation | 35 | 11.9 | 17 | 11.8 | 20 | 10.6 | 15 | 14.3 |
CNS side effects such as hallucinationsa
| 60 | 20.4 (16.0–25.5) | 29 | 20.1 (13.9–27.6) | 44 | 23.3 (17.5–30.0) | 16 | 15.2 (9.0–23.6) |
Urinary retention | 21 | 7.1 | 11 | 7.6 | 11 | 5.8 | 10 | 9.5 |
All of the above | 128 | 43.5 | 70 | 48.6 | 94 | 49.7 | 34 | 32.4 |
None of the above | 10 | 3.4 | 7 | 4.9 | 9 | 4.8 | 1 | 1.0 |
I don’t know | 40 | 13.6 | 10 | 6.9 | 11 | 5.8 | 29 | 27.6 |
Question 19: Using the Treatment Initiation Pack, by which week can the patient reach a dose of 600 mg/day? | ||||||||
2 weeks | 34 | 12.5 | 16 | 11.6 | 23 | 13.0 | 11 | 11.7 |
3 weeksa
| 153 | 56.5 (50.3–62.4) | 85 | 61.6 (52.9–69.7) | 111 | 62.7 (55.1–69.9) | 42 | 44.7 (34.4–55.3) |
4 weeks | 60 | 22.1 | 30 | 21.7 | 33 | 18.6 | 27 | 28.7 |
5 weeks | 7 | 2.6 | 1 | 0.7 | 3 | 1.7 | 4 | 4.3 |
None of the above | 17 | 6.3 | 6 | 4.3 | 7 | 4.0 | 10 | 10.6 |
Switzerlandc
| 23 | |||||||
Question 20: At what dose has Trobalt™ been shown to produce a possible QT prolonging effect? | ||||||||
600 mg | 18 | 6.6 | 10 | 7.2 | 17 | 9.6 | 1 | 1.1 |
900 mg | 16 | 5.9 | 9 | 6.5 | 8 | 4.5 | 8 | 8.5 |
1200 mga
| 121 | 44.6 (38.6–50.8) | 70 | 50.7 (42.1–59.3) | 96 | 54.2 (46.6–61.7) | 25 | 26.6 (18.0–36.7) |
1800 mg | 14 | 5.2 | 9 | 6.5 | 10 | 5.6 | 4 | 4.3 |
I don’t know | 102 | 37.6 | 40 | 29.0 | 46 | 26.0 | 56 | 59.6 |
Switzerlandb
| 23 | |||||||
Question 21: For which patients is it recommended that an ECG is recorded before initiating Trobalt™? (please select all that apply) | ||||||||
Patients with hypertension | 5 | 1.7 | 4 | 2.8 | 3 | 1.6 | 2 | 1.9 |
Patients with congestive heart failurea
| 76 | 25.9 (20.9–31.3) | 36 | 25.0 (18.2–32.9) | 55 | 29.1 (22.7–36.1) | 21 | 20.0 (12.8–28.9) |
Patients with ventricular hypertrophya
| 77 | 26.2 (21.3–31.6) | 39 | 27.1 (20.0–35.1) | 61 | 32.3 (25.7–39.4) | 16 | 15.2 (9.0–23.6) |
Patients with hypokalemiaa
| 71 | 24.1 (19.4–29.5) | 34 | 23.6 (16.9–31.4) | 57 | 30.2 (23.7–37.2) | 14 | 13.3 (7.5–21.4) |
All of the above | 178 | 60.5 | 95 | 66.0 | 118 | 62.4 | 60 | 57.1 |
None of the above | 2 | 0.7 | 1 | 0.7 | 0 | 0.0 | 2 | 1.9 |
I don’t know | 24 | 8.2 | 4 | 2.8 | 3 | 1.6 | 21 | 20.0 |
Question 22: What should you do in a patient with a QTc of more than 400 ms before starting Trobalt™? (please select the best response) | ||||||||
Recheck the ECG 1 week after the first dose | 105 | 35.7 | 56 | 38.9 | 62 | 32.8 | 43 | 41.0 |
Recheck the ECG at monthly intervals | 18 | 6.1 | 8 | 5.6 | 11 | 5.8 | 7 | 6.7 |
Recheck the ECG after reaching the maintenance dosea
| 132 | 44.9 (39.1–50.8) | 67 | 46.5 (38.2–55.0) | 106 | 56.1 (48.7–63.3) | 26 | 24.8 (16.9–34.1) |
I don’t know | 39 | 13.3 | 13 | 9.0 | 10 | 5.3 | 29 | 27.6 |
Question 23: Which new cardiac effects in particular should you warn your patients about after prescribing Trobalt™? (please select all that apply) | ||||||||
Syncope | 20 | 6.8 | 10 | 6.9 | 11 | 5.8 | 9 | 8.6 |
Palpitations | 16 | 5.4 | 11 | 7.6 | 8 | 4.2 | 8 | 7.6 |
Any other symptoms of arrhythmia | 23 | 7.8 | 12 | 8.3 | 15 | 7.9 | 8 | 7.6 |
All of the abovea
| 225 | 76.5 (71.3–81.3) | 111 | 77.1 (69.3–83.7) | 148 | 78.3 (71.7–84.0) | 77 | 73.3 (63.8–81.5) |
None of the above | 25 | 8.5 | 8 | 5.6 | 15 | 7.9 | 10 | 9.5 |