TA615/Scope Consultation Comments
Page 1

Summary form

National Institute for Health and Care Excellence

Single Technology Appraisal (STA)

Cannabidiol for adjuvant treatment of seizures associated with Dravet syndrome or Lennox-Gastaut syndrome

Response to consultee and commentator comments on the draft remit and draft scope (pre-referral)

Comment: the draft remit

Section Consultee/
Commentator		 Comments Action
Timing Issues GW Research
Ltd		 No Current treatment options for many patients with LGS and DS who are
inadequate controlled on currently available anti-epileptic drugs.		 Comment noted.

Comment: the draft scope

Section Consultee/
Commentator		 Comments Action
Background
information		 GW Research
Ltd		 Death during childhood is common in DS. Sudden unexpected death in
epilepsy (SUDEP) and Status Epilepticus (SE) are the most common causes
of death in DS, with drowning and accidental death following seizures also
common causes. Risk factors for SUDEP include frequent generalized tonic–
clonic seizures, early seizure onset, polytherapy, and developmental delay
(Sillanpää, 2010), all of which are common in DS. A recent review of 177		 Comment noted. The
background section is
intended as a brief
overview of the disease
area, therefore no
National Institute for Health and Care Excellence

Consultation comments on the draft remit and draft scope for the technology appraisal of cannabidiol for adjuvant treatment of seizures associated with Dravet syndrome or Lennox-Gastaut syndrome

Page 2

Summary form

Section Consultee/
Commentator		 Comments Action
unique cases of death in DS reported in the literature highlighted that 73% of
the deaths occurred before the patient reached 10 years of age, with the
cause being SUDEP in 49% of cases, and SE in 32% of cases (Shmuely,
2016). Longitudinal follow-up (median 17 years) of 100 unrelated DS patients
enrolled into the Epilepsy Genetics Research Program reported 17 deaths
with a median patient age of 7 years, equating to a DS specific mortality rate
of 15.84 per 1000 patient years (Cooper, 2016). SUDEP was the most
common cause of death (59%), equating to a DS-specific SUDEP rate of 9.32
per 1000 patient years, which is nearly twice the rate for adults with refractory
epilepsy.
Cooper MS, Mcintosh A, Crompton DE, Schneider A, McMahon JM,
Schneider A et al. Mortality in Dravet syndrome. Epilepsy Res. 2016; 128:43-
47.
Shmuely S (2016) Mortality in Dravet syndrome: A review Epilepsy and
Behaviour. Epilepsy & Behavior 64, 69–¬74
Sillanpää and Shinnar, Long-term Mortality in Childhood-Onset Epilepsy. N
Engl J Med 2010; 363:2522-2529		 amendments required.
The technology/
intervention		 GW Research
Ltd		 The precise mechanisms by which cannabidiol exerts its anticonvulsant
effects in humans are unknown. Cannabidiol reduces neuronal
hyperexcitability and inflammation through modulation of intracellular calcium
via GPR55 and TRPV1 channels and modulation of adenosine-mediated		 Comment noted. The
scope has been
amended to reflect the
expected mechanism of

National Institute for Health and Care Excellence

Consultation comments on the draft remit and draft scope for the technology appraisal of cannabidiol for adjuvant treatment of seizures associated with Dravet syndrome or Lennox-Gastaut syndrome

Page 3

Summary form

Section Consultee/
Commentator		 Comments Action
signalling. action.
Population GW Research
Ltd		 LGS accounts for 1 to 4% of childhood epilepsies, and 10% of epilepsies
starting in children under the age of 5 years.
LGS prevalence has been estimated at 0.9 per 10,000 population of all ages,
and an incidence of 2 new cases per 100,000 children aged 0 to 14 years per
year.
Extrapolating statistics for the United Kingdom from the Office for National
Statistics in 2016[ONS 2016], we can calculate that the likely number of
patients with LGS will be as shown in Table below;
England
Total population 2016
55,268,100
Population aged 0-14
years 2016
9,927,600
Prevalence of LGS
4,974		 Comment noted.

National Institute for Health and Care Excellence

Page 3 of 5 Consultation comments on the draft remit and draft scope for the technology appraisal of cannabidiol for adjuvant treatment of seizures associated with Dravet syndrome or Lennox-Gastaut syndrome

Page 4

Summary form

Section Consultee/
Commentator		 Comments Comments Action
Incidence in children
aged 0-14 years		 199
Outcomes GW Research
Ltd		 Include in the outcome measures; change in drop seizures (defined as tonic-
clonic, tonic or atonic seizures that led, or could have led, to a fall or injury).
Care Giver Impression of Change measuring improvement in patient’s quality
of life from the care giver and/or physician perspective is relevant in this case
due to the lack of developmental progression in the majority of these patients.		 Comment noted. At the
scoping workshop it
was noted that ‘change
in drop seizures’ would
be captured by the
outcome ‘seizure
frequency (by seizure
type)’. Care giver-
related quality could be
considered under
health-related quality of
life or could be captured
within the innovation
section.
Other Association of Important to ensure adults with these conditions are included in the scoping Comment noted.

National Institute for Health and Care Excellence

Consultation comments on the draft remit and draft scope for the technology appraisal of cannabidiol for adjuvant treatment of seizures associated with Dravet syndrome or Lennox-Gastaut syndrome Issue date: October 2018

Page 5

Summary form

Section Consultee/
Commentator		 Comments Action
considerations British
Neurologists		 workshop
Important to ensure if the agent is taken forward for further consideration,
barriers to access do not become onerous, as is currently the case (for
example) for stiripentol use in adults with Dravet Syndrome (with particular
current difficulties when children on the drug reach the age of 18, for
example, or if stiripentol needs to be started after the age of 18 years, when
the condition is the same as it was before the patient's 18th birthday)		 Guidance will only be
issued in accordance
with the marketing
authorisation. At the
scoping workshop the
clinical experts noted
that they did not expect
any differences in
clinical management
between adults and
children.

The following consultees/commentators indicated that they had no comments on the draft remit and/or the draft scope

Department of Health

National Institute for Health and Care Excellence

Consultation comments on the draft remit and draft scope for the technology appraisal of cannabidiol for adjuvant treatment of seizures associated with Dravet syndrome or Lennox-Gastaut syndrome