RedCAP data current as of 2022-08-31 13:45:34

1 Project overview

1.1 Background

Epidiolex is used to treat patients 2 years of age or older with Lennox Gastaut Syndrome or Dravet Syndrome. VSP gained access to Epidiolex in January 2019. Typical steps in the process for patients to initiate therapy are prior authorization (PA) submission, obtainment of insurance approval (sometimes involves an appeal), medication counseling, and medication shipment.

1.2 Methods

Patients who were prescribed prescription cannabidiol by a Vanderbilt Medical Center provider between January 1, 2019 and April 30, 2020 were included in the sample. There is no pre- and post-access comparator group available.

1.3 Outcomes

Clinical Characteristics

  • Demographic characteristics of study population (age, sex, race, ethnicity, height/weight, diagnosis)
  • Prior AED therapies trialed (number, type)
  • Previous non-pharmacological treatments trialed (dietary, surgical, VNS, DBS)
  • Obtainment of baseline HFP
  • Reason for therapy initiation (patient versus provider request)
  • Route of administration
  • Number and type of concurrent AED therapies upon Epidiolex initiation
  • Number and type of drug-drug interactions present upon Epidiolex initiation

Access

  • Time to prior authorization approval or denial from date of patient referral to specialty pharmacy services
  • Time to completion of insurance coverage appeal, if applicable, from date of prior authorization denial
  • Percentage of patients who are referred to manufacturer patient assistance program (PAP)
  • Rate of utilization of other financial assistance modalities
  • Time to medication access: number of days from date of decision to treat and date of medication shipment (time from [date_bi] to [ship_date])

2 Exclusions

Exclusions
N
N=160
Reason for exclusion 160
    Participation in clinical trial 1.2% ( 2)
    Receiving medication through manufacturer 0.6% ( 1)
    Receiving from external specialty pharmacy 10.6% ( 17)
    VSP did not complete PA process 2.5% ( 4)
    No exclusion criteria met. Patient should be INCLUDED in the study. 85.0% (136)
N is the number of non-missing values. Numbers after proportions are frequencies.

3 Descriptive statistics

3.1 Demographics

Demographics
N
 Adult
N=44		 Pediatric
N=92		 Combined
N=136
Age at start of prescription therapy 136 21.2 27.5 43.9  (32.8 ±13.3) 4.6 10.0 13.8  ( 9.5 ± 5.1) 8.6 13.8 20.9  (17.1 ±13.9)
Patient age category 136
    Adult 100% (44) 0% ( 0) 32% (44)
    Pediatric 0% ( 0) 100% (92) 68% (92)
Gender 136
    Female 57% (25) 47% (43) 50% (68)
    Male 43% (19) 53% (49) 50% (68)
Race 136
    White 86.4% ( 38) 83.7% ( 77) 84.6% (115)
    Black or African American 11.4% ( 5) 10.9% ( 10) 11.0% ( 15)
    Other Asian 0.0% ( 0) 1.1% ( 1) 0.7% ( 1)
    Decline to Answer 2.3% ( 1) 0.0% ( 0) 0.7% ( 1)
    Unknown 0.0% ( 0) 4.3% ( 4) 2.9% ( 4)
Insurance type 136
    Commercial 22.7% (10) 19.6% (18) 20.6% (28)
    Medicare 45.5% (20) 0.0% ( 0) 14.7% (20)
    Medicaid 31.8% (14) 72.8% (67) 59.6% (81)
    Tricare 0.0% ( 0) 7.6% ( 7) 5.1% ( 7)
    Other 0.0% ( 0) 0.0% ( 0) 0.0% ( 0)
Height (cm) 122 153 164 173  (163 ± 15) 102 130 147  (126 ± 30) 120 146 163  (139 ± 31)
Weight (kg) 136 49 62 76  (67 ±24) 17 29 38  (34 ±23) 24 37 60  (44 ±28)
a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. x ± s represents X ± 1 SD.   N is the number of non-missing values. Numbers after proportions are frequencies.

3.1.1 Age, height and weight

3.1.1.1 Pediatric

3.1.1.2 Adult

3.2 Medications

3.2.1 Previous medications

Previous medications
N
N=136
Number of previous medications 136 5.0 7.0 11.0  ( 8.2 ± 4.1)
Number of previous medications 136
    2 2.9% ( 4)
    3 5.1% ( 7)
    4 8.8% (12)
    5 14.7% (20)
    6 8.1% (11)
    7 12.5% (17)
    8 8.1% (11)
    9 3.7% ( 5)
    10 8.8% (12)
    11 5.9% ( 8)
    12 6.6% ( 9)
    13 1.5% ( 2)
    14 5.1% ( 7)
    15 1.5% ( 2)
    16 2.2% ( 3)
    17 1.5% ( 2)
    18 2.2% ( 3)
    21 0.7% ( 1)
a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. x ± s represents X ± 1 SD.   N is the number of non-missing values. Numbers after proportions are frequencies.

3.2.2 Previous non-pharmacological treatments trialed

Previous non-pharm
N
N=136
Previous non-pharmacological treatments trialed 68
    Deep brain stimulation (DBS) 1.5% ( 1)
    Ketogenic diet 36.8% (25)
    Surgery 4.4% ( 3)
    Surgery, Ketogenic diet 2.9% ( 2)
    Surgery, Vagal nerve stimulation (VNS) 11.8% ( 8)
    Surgery, Vagal nerve stimulation (VNS), Ketogenic diet 8.8% ( 6)
    Vagal nerve stimulation (VNS) 14.7% (10)
    Vagal nerve stimulation (VNS), Ketogenic diet 19.1% (13)
N is the number of non-missing values. Numbers after proportions are frequencies.

3.2.3 Drug-drug interactions at baseline

Interactions
N
N=136
Number of drug-drug interactions 109 1.0 2.0 3.0  (2.2 ±1.3)
Number of drug-drug interactions 109
    1 42.2% (46)
    2 25.7% (28)
    3 15.6% (17)
    4 9.2% (10)
    5 4.6% ( 5)
    6 2.8% ( 3)
a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. x ± s represents X ± 1 SD.   N is the number of non-missing values. Numbers after proportions are frequencies.

3.2.4 Concurrent medications at start

Concurrent medications
N
N=136
Number of concurrent medications 132 2.0 3.0 4.0  (2.8 ±1.2)
Number of concurrent medications 132
    1 15.2% (20)
    2 28.8% (38)
    3 25.8% (34)
    4 25.0% (33)
    5 3.8% ( 5)
    6 1.5% ( 2)
a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. x ± s represents X ± 1 SD.   N is the number of non-missing values. Numbers after proportions are frequencies.

3.3 Drug Drug interactions at baseline management

Management
N
 Adult
N=44		 Pediatric
N=92		 Combined
N=136
Route of administration 136
    By mouth (PO) 93.2% ( 41) 78.3% ( 72) 83.1% (113)
    G-tube 6.8% ( 3) 18.5% ( 17) 14.7% ( 20)
    Other 0.0% ( 0) 3.3% ( 3) 2.2% ( 3)
Was management of a possible drug interaction performed at baseline (prior to starting prescription CBD)? 136
    No 25% ( 11) 17% ( 16) 20% ( 27)
    Yes 75% ( 33) 83% ( 76) 80% (109)
What type of drug interaction was managed? 109
    Pharmacokinetic 9.1% ( 3) 25.0% (19) 20.2% (22)
    Pharmacodynamic 42.4% (14) 36.8% (28) 38.5% (42)
    Both 48.5% (16) 38.2% (29) 41.3% (45)
N is the number of non-missing values. Numbers after proportions are frequencies.

4 Previous meds

4.1 Totals

4.2 Figure

5 Concurrent medications

6 Previous non-pharmacological treatments trialed

6.1 Totals

6.2 Intersection

Pediatric

7 Number and type of drug-drug interactions present upon Epidiolex initiation

8 Outcome of drug interaction management

8.1 Agents and outcomes

Outcomes of drug interaction management
Agent n.agent Outcome n pct.outcome
clobazam 63 other agent stopped 1 1.6%
other agent dose change 5 7.9%
no medication change needed, pharmacist provided counseling only 57 90.5%
benzodiazepine (such as clonazepam, diazepam, lorazepam, midazolam) 58 no medication change needed, pharmacist provided counseling only 58 100.0%
antiepileptic medication not noted above 55 other agent stopped 3 5.5%
no medication change needed, pharmacist provided counseling only 52 94.5%
valproic acid 26 other agent dose change 1 3.8%
no medication change needed, pharmacist provided counseling only 25 96.2%
artisinal CBD 18 other agent stopped 18 100.0%
antihistamine (such as cetirizine, diphenhydramine, loratadine, fexofenadine) 9 no medication change needed, pharmacist provided counseling only 9 100.0%
antipsychotic 6 no medication change needed, pharmacist provided counseling only 6 100.0%
phenobarbital 5 no medication change needed, pharmacist provided counseling only 5 100.0%
antidepressant 4 no medication change needed, pharmacist provided counseling only 4 100.0%
fluoxetine no medication change needed, pharmacist provided counseling only 4 100.0%
other no medication change needed, pharmacist provided counseling only 4 100.0%
muscle relaxer 2 no medication change needed, pharmacist provided counseling only 2 100.0%
promethazine no medication change needed, pharmacist provided counseling only 2 100.0%
carbamazepine 1 no medication change needed, pharmacist provided counseling only 1 100.0%
cyproheptadine no medication change needed, pharmacist provided counseling only 1 100.0%
meclizine no medication change needed, pharmacist provided counseling only 1 100.0%
mTor inhibitor (everolimus, tacrolimus) no medication change needed, pharmacist provided counseling only 1 100.0%

8.2 Patient level summary

Patient level DI outcome management instances
Overall
(N=109)
n
mean (sd) 2.39 (± 1.68)
med (iqr) 2.00 [1.00, 3.00]
min, max [1.00, 8.00]
count
1 46 (42.2%)
2 24 (22.0%)
3 16 (14.7%)
4 10 (9.2%)
5 5 (4.6%)
6 4 (3.7%)
7 3 (2.8%)
8 1 (0.9%)
pkpd
Both 45 (41.3%)
Pharmacodynamic 42 (38.5%)
Pharmacokinetic 22 (20.2%)

8.3 Agents

Summary of agents
Overall
(N=260)
Agent
clobazam 63 (24.2%)
benzodiazepine (such as clonazepam, diazepam, lorazepam, midazolam) 58 (22.3%)
antiepileptic medication not noted above 55 (21.2%)
valproic acid 26 (10.0%)
artisinal CBD 18 (6.9%)
antihistamine (such as cetirizine, diphenhydramine, loratadine, fexofenadine) 9 (3.5%)
antipsychotic 6 (2.3%)
phenobarbital 5 (1.9%)
antidepressant 4 (1.5%)
fluoxetine 4 (1.5%)
other 4 (1.5%)
muscle relaxer 2 (0.8%)
promethazine 2 (0.8%)
carbamazepine 1 (0.4%)
cyproheptadine 1 (0.4%)
meclizine 1 (0.4%)
mTor inhibitor (everolimus, tacrolimus) 1 (0.4%)

8.4 Outcomes

Summary of outcomes
Overall
(N=260)
Outcome
no medication change needed, pharmacist provided counseling only 232 (89.2%)
other agent stopped 22 (8.5%)
other agent dose change 6 (2.3%)

8.5 PK/ PD

Characteristic N N = 2601
new_di_type 260
Pharmacodynamic 184 (70.8%)
Pharmacokinetic 76 (29.2%)
1 n (%)

9 Obtainment of baseline hepatic function panel (HFP)

9.1 Figure

10 Liver function labs

Characteristic N N = 2981
AST result 298
High 99 (33.2%)
In range 186 (62.4%)
Low 12 (4.03%)
Not available 1 (0.34%)
ALT result 298
High 83 (27.9%)
In range 201 (67.4%)
Low 11 (3.69%)
Not available 1 (0.34%)
Undetectable 2 (0.67%)
Bili result 298
High 37 (12.4%)
In range 229 (76.8%)
Low 6 (2.01%)
Not available 6 (2.01%)
Undetectable 20 (6.71%)
1 n (%)

11 Discontinuation

11.1 Discontinuation summary

Characteristic N N = 1361
Did the patient discontinue medication 136
No 95 (69.9%)
Yes 41 (30.1%)
Time to discontinuation 41
Mean (SD) 234.6 (185.3)
Median (IQR) 181.0 (81.0 - 349.0)
Range 13.0 - 657.0
Missing 95
1 n (%)

11.2 Figures

11.3 DC reasons

11.3.1 Reasons for DC

The denominator here is 41

value n pct
No response/sub-optimal response to therapy 15 36.6%
Common side effects 14 34.1%
Major side effects/complication 14 34.1%
Patient Decision (Not related to side effects/financial limitations) 4 9.8%
Non-compliance 3 7.3%
Deceased 2 4.9%
NULL/Data not available 2 4.9%

11.3.2 AEs listed as reason for DC

Here, the denominator is 20: the number of people reporting side effects as a reason for discontinuation (Major side effects/complication or Common side effects)

value n pct
Aggressive behavior 4 20%
Agitation/ irritability 4 20%
Mood changes 4 20%
Behavioral changes 3 15%
Drowsiness 3 15%
Increased seizure frequency 3 15%
Insomnia or sleep disturbance 3 15%
Self-injurious behaviors 3 15%
GI upset 2 10%
Sialorrhea 2 10%
Appetite changes 1 5%
Gait disturbances 1 5%
Headaches 1 5%
Hot flashes 1 5%
Lethargy 1 5%
LFT elevation 1 5%
Low body temperature 1 5%
Mental status change 1 5%
Musculoskeletal 1 5%
Rash 1 5%
Sedation 1 5%
Serum/urine abnormalities 1 5%
Suicidal ideation 1 5%

12 Adverse events

value n pct
Drowsiness 30 22.1%
GI upset 21 15.4%
Sedation 14 10.3%
Agitation/ irritability 9 6.6%
Lethargy 9 6.6%
Insomnia or sleep disturbance 8 5.9%
Gait disturbances 7 5.1%
Aggressive behavior 6 4.4%
Decreased appetite 6 4.4%
Sialorrhea 5 3.7%
LFT elevation 4 2.9%
Fatigue 3 2.2%
Mood changes 3 2.2%
Appetite changes 2 1.5%
Behavioral changes 2 1.5%
Depression 2 1.5%
Mental status change 2 1.5%
Musculoskeletal 2 1.5%
Rash 2 1.5%
Serum/urine abnormalities 2 1.5%
Dizziness 1 0.7%
Headaches 1 0.7%
Hot flashes 1 0.7%
Hyperactivity 1 0.7%
Increased seizure frequency 1 0.7%
Polydipsia 1 0.7%
Polyuria 1 0.7%
Tachycardia 1 0.7%
Urinary incontinence 1 0.7%
Visual changes 1 0.7%

13 Financial assistance