Suffolk PCT Drug & Therapeutics Committee
New Medicine Report
This drug has been reviewed because it is a product that may be prescribed in primary care
Medicine
Brimonidine tartrate gel (Mirvaso®) for the treatment of facial erythema
Document status
Final draft for consideration by the D&T 08/12/14.
Reviewed at Suffolk CCGs D&TC 27 January 2015 and CPG 9 March 2015.
05/11/14
Date of last
revision
Traffic light
decision
Prescriber rating
Proposed Sector of
prescribing
Double red – no prescribing
N/A
Primary and Secondary Care
This evidence review is based on the NICE new medicine summary – Facial erythema of rosacea:
Brimonidine tartrate, published 08 July 2014. The full summary can be accessed at
http://www.nice.org.uk/Advice/ESNM43
Introduction
Introduction
Rosacea is a chronic relapsing disease of facial skin, characterised by recurrent
Summary Key
episodes of facial flushing, persistent erythema, telangiectasia (fine, dilated blood
points
vessels), papules and pustules. For the symptoms of flushing and erythema
1
Evidence level
(without papules and pustules) there is historically no effective treatment in primary
care, and management generally consists of lifestyle advice, including applying
sunscreen and avoiding trigger factors when practical. Brimonidine tartrate gel
(Mirvaso®) is the first medicinal product to be approved for the symptomatic
treatment of facial erythema of rosacea.
Summary
In 2 short-term randomised controlled trials (RCTs: n=553) brimonidine tartrate gel
was statistically significantly more effective than vehicle gel in reducing erythema in
people with a clinical diagnosis of rosacea and moderate to severe erythema.
However, 'success rates' (defined as a 2-grade reduction in the severity of
erythema as assessed by both patients and clinicians) were just 25% to 30% with
brimonidine gel compared with about 10% for vehicle gel at day 29. In addition,
interaction studies are lacking and there is weak data to support the use of
brimonidine gel in patients using other topical products concomitantly.
Key Points:Effectiveness
In 2 RCTs (n=553), compared with
vehicle gel:
 a statistically significantly greater
'success rate' (2-grade reduction
in severity of erythema) was seen
with brimonidine tartrate gel (about
25% to 30% with brimonidine
compared with about 10% for
vehicle at day 29; p<0.001).
 a statistically significantly greater
Page 1 of 12
Safety
 Brimonidine tartrate gel is
contraindicated in people receiving
monoamine oxidase inhibitors,
tricyclic or tetracyclic
antidepressants, and in children
aged less than 2 years.
 The summary of product
characteristics states that no
clinically meaningful trends in
tachyphylaxis or rebound effects
'responder rate' (1-grade reduction
(worsening of erythema after
in severity of erythema) was seen
stopping treatment) were seen
with brimonidine tartrate gel (about
with the use of brimonidine tartrate
70% with brimonidine compared
gel for 29 days, but a report of 3
with about 30% to 40% with
people with possible rebound
vehicle at day 29; p<0.001).
erythema has been published.
 a rapid onset of effect is seen with
brimonidine tartrate gel (within 30
minutes in 28% of people), which
peaks at about 3 hours and is
partially maintained over a 12-hour
period.
Patient factors
Resource implications
 At day 29, about 40% of people
 Brimonidine tartrate gel is £33.69
using brimonidine tartrate gel were
for a 30 g tube (excluding VAT;
'satisfied' or 'very satisfied' and
cost taken from MIMS, May 2014).
about 26% of people were
 The maximum daily recommended
'dissatisfied' or 'very dissatisfied'
dose is 1 g of gel (Brimonidine
with their appearance (2 RCTs,
tartrate gel [Mirvaso®]. In a longn=553).
term study the average daily
 Brimonidine tartrate gel is
amount used was 0.5 g.
generally well tolerated; the
summary of product
characteristics states that the most
common adverse reactions are
erythema, pruritus, flushing and
skin burning sensation (occurring
in between 1.2% and 3.3% of
people in clinical studies).
 Brimonidine tartrate gel is a
symptomatic treatment with a
transient effect on erythema. It
does not alter the course of the
disease of have any effect on
other features of rosacea. It can
be used up to once per day, on a
daily or as-required basis.
 Both RCTs were short-term (4-week treatment phase and 4-week follow-up
phase) and compared brimonidine tartrate gel with vehicle gel, not an active
comparator. They were conducted in people with moderate to severe erythema
(marked or fiery redness), and there is no evidence for the use of brimonidine
tartrate gel in people with less severe erythema.
 Long-term efficacy and safety data are limited to those available from an openlabel, non-comparative study, which followed people for up to 12 months
(Moore et al. 2014).
 Efficacy end points for erythema of rosacea are not clearly established. The
CEA and PSA scales used in the brimonidine tartrate gel trials are novel scales
based on subjective judgements, not objective measures, and defining what a
clinically important change is on these scales is difficult.
The intervention
Mechanism of
action1
Licensed
indication*2
Formulation/Availa
ble Products*2
Brimonidine tartrate is a highly selective alpha-2 adrenergic receptor antagonist
with potent vasoconstrictive and vasostabilising activity.
Brimonidine tartrate gel is indicated for the symptomatic treatment of facial
erythema of rosacea in adult patients.
Brimonidine tartrate gel (Mirvaso®) 3 mg/g gel
One gram of gel contains 3.3 mg of brimonidine, equivalent to 5 mg of brimonidine
tartrate.
Page 2 of 12
Excipient(s) with known effect:
One gram of gel contains 1 mg methylparahydroxybenzoate (E218) and 55 mg
propylene glycol.
Usual dosage*2
One application per 24 hours, at any time suitable for the patient, for as long as
facial erythema is present.
The maximum daily recommended dose is 1 g of gel in total weight, divided into five
pea size amounts.
Special populations
Elderly patients
The experience of use of Brimonidine tartrate gel in patients aged above 65 years
is limited.
Paediatric population
The safety and efficacy of Brimonidine tartrate gel in children and adolescents aged
less than 18 years have not been established. No data are available.
Brimonidine tartrate gel is contraindicated in children aged less than 2 years
because of serious systemic safety risk. Safety concerns related to the systemic
absorption of brimonidine have also been identified for the age group 2 to 12 years.
Brimonidine tartrate gel should not be used in children or adolescents aged 2 to 18
years.
Method of administration
Cutaneous use only.
Cutaneous application of a small pea size amount of medicinal product to each of
the five areas of the face: forehead, chin, nose, each cheek.
Brimonidine tartrate gel should be applied smoothly and evenly as a thin layer
across the entire face avoiding the eyes, eyelids, lips, mouth and membrane of the
inner nose. It should be applied only to the face.
Hands should be washed immediately after applying the medicinal product.
Brimonidine tartrate gel can be used in conjunction with other cutaneous medicinal
products for the treatment of inflammatory lesions of rosacea and with cosmetics.
These products should not be applied immediately before the daily application of
brimonidine tartrate gel; they may be used only after the brimonidine tartrate gel
applied has dried.
Treatment
alternatives/ place
in therapy1
Future alternatives5
Page 3 of 12
Management of facial erythema of rosacea generally consists of lifestyle advice.
Off-label propranolol or clonidine may be used to treat flushing but this use is not
supported by evidence from RCTs. For persistent erythema or telangiectasia, laser
therapy can be effective although improvement is not permanent, and this may not
be available on the NHS. Camouflage cream is also used.
Mild or moderate papulopustular rosacea is usually treated with topical
metronidazole or azelaic acid. The activity of these drugs on underlying erythema
and flushing is based reduction of inflammatory redness and long term action on
small vessels, but they provide no immediate and evident improvement on baseline
erythema that can be evident in the short term.
For moderate or severe papulopustular rosacea, oral tetracycline, erythromycin,
doxycycline or lymecycline can be prescribed, although not all of these drugs are
licensed for treating rosacea and RCT data to support their use are limited.
Ivermectin (antiparasitic agent) is in phase III Clinical Trials. (Source New Drugs
online data base http://www.ukmi.nhs.uk/applications/ndo/record_view.asp?newDrugID=5617
National guidance1
Not on the NICE work programme.
Local Guidance
Evidence for use1
Contraindications
and Precautions*2
Page 4 of 12
This evidence summary is based on 2 short-term, randomised, vehicle-controlled
phase III trials of identical design (trial A [n=260] and trial B [n=293]) of brimonidine
tartrate gel in adults with a clinical diagnosis of rosacea and moderate to severe
erythema (Fowler et al. 2013).
In both RCTs, brimonidine tartrate gel was statistically significantly more effective
than vehicle gel in reducing erythema.
 For the primary end point of 'success rate', defined as a 2-grade improvement
on both the 5-point Clinician's Erythema Assessment (CEA) and the 5-point
Patient's Self-Assessment (PSA) of erythema over 12 hours, the 'success rate'
at day 29 (3 hours after application) was 31.5% with brimonidine gel and 10.9%
with vehicle gel in trial A, and 25.4% with brimonidine gel and 9.2% with vehicle
gel in trial B (both p<0.001 over 12 hours).
 The secondary end point of onset of efficacy (the '30-minute effect'), defined as
a 1-grade improvement from baseline on both the CEA and PSA at 30 minutes
on day 1, was seen in 27.9% of the brimonidine gel group and 6.9% of the
vehicle gel group in trial A and 28.4% of the brimonidine gel group and 4.8% of
the vehicle gel group in trial B (both p<0.001).
 At day 29 (3 hours after application), the 'responder rate' for a 1-grade
improvement on both the CEA and PSA was 70.9% with brimonidine gel and
32.8% with vehicle gel in trial A, and 71.1% with brimonidine gel and 40.1%
with vehicle gel in trial B (both p<0.001 over 12 hours).
 At day 29, more people were 'satisfied' or 'very satisfied' with their appearance
in the brimonidine gel groups than in the vehicle gel groups (no statistical
analysis reported), and statistically significantly more people in the brimonidine
gel groups reported overall improvement in erythema compared with those in
the vehicle gel groups (p<0.001).However, a substantial number of people were
not satisfied with their appearance. At day 29, 27.6% of people in the
brimonidine gel group compared with 43.7% of people in the vehicle gel group
were 'dissatisfied' or 'very dissatisfied' in trial A and 24.6% of people in the
brimonidine gel group compared with 42.2% in the vehicle gel group were
'dissatisfied' or 'very dissatisfied' in trial B (no statistical analysis reported).
Two further studies have been completed but the results are not yet published.
These are the Patient-Reported Outcome of Facial Erythema (PROOF) study, and
an RCT comparing brimonidine tartrate gel with azelaic acid gel (ClinicalTrials.gov
identifier: NCT01659853).
Contraindications: Hypersensitivity to the active substance or to any of the excipients.
 Children aged less than 2 years.
 Patients receiving monoamine oxidase (MAO) inhibitor therapy (for example
selegiline or moclobemide) and patients on tricyclic (such as imipramine) or
tetracyclic (such as maprotiline, mianserin or mirtazapin) antidepressants which
affect noradrenergic transmission.
Precautions:Brimonidine tartrate gel should not be applied on irritated skin or open wounds, or
close to the eyes. In the case of severe irritation or contact allergy, treatment
should be discontinued. Any increase in the daily amount applied and/or frequency
of application should be avoided, because the safety of higher daily doses or
repeated daily application has not been assessed.
The concomitant use of other systemic alpha adrenergic receptor agonists may
potentiate the undesirable effects of this class of medicinal products in patients:
- with severe or unstable or uncontrolled cardiovascular disease;
- with depression, cerebral or coronary insufficiency, Raynaud's phenomenon,
orthostatic hypotension, thrombangiitis obliterans, scleroderma, or Sjögren's
syndrome.
The medicinal product contains methylparahydroxybenzoate (E218) which may
cause allergic reactions (possibly delayed), and propylene glycol which may cause
skin irritation.
Safety and
Tolerability*1,2
Drug Interactions*2
Pregnancy and
lactation*2
Page 5 of 12
In both RCTs, 0.5% brimonidine tartrate gel was generally well tolerated. Adverse
events occurred in 29.5% of people in the brimonidine gel group and 25.2% of
people in the vehicle gel group in trial A, and in 33.8% of the brimonidine gel group
and 24.1% of the vehicle gel group in trial B (no statistical analysis reported).
Treatment-related adverse events were less frequent, occurring in 11.6% and 9.5%
of the brimonidine gel groups in trial A and B respectively, and in 5.3% and 9.7% of
the vehicle gel groups (no statistical analyses reported). In trial A, 2 people
(1.6%) discontinued because of an adverse event in the active group compared
with 1 person (0.8%) in the vehicle group; in trial B, 1 person (0.7%) discontinued
because of an adverse event in each group (Fowler et al. 2013).
The brimonidine tartrate gel summary of product characteristics states that the most
commonly reported adverse reactions are erythema, pruritus, flushing and skin
burning sensation, all occurring in between 1.2% and 3.3% of people in clinical
studies. They are typically mild to moderate in severity, and usually do not require
discontinuation of treatment.
The summary of product characteristics states that no clinically meaningful trends
with respect to tachyphylaxis or rebound effects (worsening of erythema after
stopping treatment) were seen with the use of brimonidine tartrate gel for 29 days.
However, a report of severe erythema and burning sensation in 3 people using
brimonidine tartrate gel has recently been published (Routt et al. 2014). The
authors state that these could be rebound vasodilation reactions to brimonidine,
similar to rebound nasal congestion seen with overuse of alpha-adrenergic agonist
nasal sprays. They suggest that counselling people about the potential for
worsening erythema, use of a test area, and limiting use to special occasions may
be warranted. An additional case report (Ilkovitch D et al) in one patient noted facial
erythema which occurred 12 hours after application of brimonidine gel. This
erythema was significantly increased from baseline and this increased rebound
erythema lasted for an additional 12 to 14 hours before facial erythema regressed
to baseline. The authors note that although this significant rebound erythema
appears to be temporary, patients should be counselled on the potential sideeffect.7
No interaction studies have been performed.
 Brimonidine gel is contraindicated in patients receiving monoamine oxidase
(MAO) inhibitor therapy and patients on tricyclic or tetracyclic antidepressants
which affect noradrenergic transmission.
 The possibility of an additive or potentiating effect with central nervous system
depressants (alcohol, barbiturates, opiates, sedatives, or anaesthetics) should
be considered.
 No data on the level of circulating catecholamines after brimonidine gel
administration are available. Caution, however, is advised in patients taking
substances which can affect the metabolism and uptake of circulating amines
e.g. chlorpromazine, methylphenidate, reserpine.
 Caution is advised when initiating (or changing the dose of) a concomitant
systemic substance (irrespective of pharmaceutical form) which may interact
with alpha adrenergic receptor agonists or interfere with their activity i.e.
agonists or antagonists of the adrenergic receptor e.g. (isoprenaline, prazosin).
 Brimonidine may cause clinically insignificant decreases in blood pressure in
some patients. Caution is therefore advised when using medicinal products
such as anti-hypertensives and/or cardiac glycosides concomitantly with
brimonidine.
As a precautionary measure, it is preferable to avoid the use of brimonidine gel
during pregnancy.
Brimonidine gel should not be used during breast-feeding.
Costs
Tariff status
Activity costs
See also section on ‘treatment alternatives/ place in therapy’ above.
Drug & Strength
Usual usea
Cost (Excluding VAT)
Metronidazole 0.75%
Thin layer applied to
1 x 30g: £6.60 to £12.00c
gelb
affected skin areas twice 1 x 40g: £9.88 to £22.63c
daily.
Metronidazole 0.75%
Thin layer applied to
1 x 30g: £6.60d
creamb
affected skin areas twice 1 x 40g: £9.98d
daily.
Azelaic acid 15% gelb
Applied to affected skin
1 x 30g: £7.48d
areas twice daily
Brimonidine tartrate
Thin layer applied to
1 x30g: £33.69c
0.5% gel
entire face once daily.
a Taken
from the summaries of product characteristics. These directions do not
represent the full range that can be used and they do not imply therapeutic
equivalence.
b The activity of these drugs on underlying erythema and flushing is based on
reduction of inflammatory redness and long term action on small vessels, but they
provide no immediate and evident improvement of baseline erythema that can be
evident in the short term.
c Costs taken from MIMS, May 2014
d Costs taken from Drug Tariff, May 2014
e The maximum daily recommended dose is 1 g of gel in total weight, divided into 5
pea-sized amounts (applied to each of the 5 areas of the face: forehead, chin, nose
and each cheek. In the long-term study, the average daily amount used was
0.532g. On this basis, a 30g tube will last for approximately 2 months and the
annual cost per patient would be £202.
Cost effectiveness
(if available)
Impact per 100,000
population
Affordability
considerations
No assessment available.
Incidence rate for diagnosed rosacea in the UK is 1.65 per 1,000 person-years.
Rosacea is diagnosed in 80% of cases after the age of 30 years. Ocular symptoms
are recorded in 21% of cases. (Source – New Drugs online
http://www.ukmi.nhs.uk/applications/ndo/record_view.asp?newDrugID=5932)4
The NICE New Evidence Summary states that it is not possible to provide
estimated usage based on available data.
The following information comes from the Summary of Potential Financial
Implications of New Drug Introductions for the 2014/15 Financial Year, produced by
Bedfordshire Clinical Commissioning Group, February 2014.3
If it is assumed that 50% of these patients are eligible for treatment with
brimonidine topical gel and cost is £33/patient/month, this could result in an
additional cost implication of ~£33,000 per 100,000 population. If usage is only
15g/patient per month, the additional cost implication would be ~ £16,500 per
100,000 population.
Page 6 of 12
Decisions from
other bodies
All Wales Medicines Strategy Group – Advice:
‘In the absence of a submission from the holder of the marketing authorisation,
brimonidine (Mirvaso®) cannot be endorsed for use within NHS Wales for the
symptomatic treatment of facial erythema of rosacea in adult patients.’
http://www.awmsg.org/awmsgonline/app/appraisalinfo/2168 6
Scottish Medicines Consortium – not assessed (and no assessment planned).
Comments sought
from –
Consultant Dermatologists, East of England Provider Trusts
Local feedback
From: Mahmood, Khalid
I feel this is a good addition to rosacea treatment; we did not have anything to help
with redness apart from laser which unfortunately is not available on NHS. I shall
support inclusion in the formulary.
Evidence strengths
and limitations1
Dr Mahmood, ,Ipswich Hospital NHS Trust
The 2 randomised, vehicle-controlled phase III trials (Fowler et al. 2013) were welldesigned and well-conducted, with no major differences between the active
treatment and the vehicle groups in baseline characteristics. In both trials, patients
and clinicians were blinded to which treatment they were given, but some degree of
unblinding was possible because of the clinical effects of brimonidine on the skin.
Both trials were short-term (4-week treatment phase and 4-week follow-up phase)
and compared brimonidine tartrate gel with vehicle gel, not an active comparator;
although, because there are no approved medicinal products in Europe that directly
target facial erythema of rosacea, this is probably reasonable. Long-term efficacy
and safety data are limited to that available from the open-label, non-comparative
study, which followed people for up to 12 months (Moore et al.2014).
Brimonidine tartrate gel is licensed for the symptomatic treatment of facial
erythema of rosacea in adults (Brimonidine tartrate gel [Mirvaso] summary of
product characteristics). However, the 2 RCTs and the open-label study were
conducted in people with moderate to severe erythema (marked or fiery
redness) according to both the CEA and PSA. There is no evidence for the
use of brimonidine tartrate gel in people with less severe erythema, which
could represent a substantial proportion of the primary care population.
The European public assessment report for Mirvaso (EPAR) states that there is no
European guideline available for products indicated for the treatment of rosacea,
and efficacy end points are not clearly established. Therefore, the manufacturer
developed the clinician assessment (CEA) and patient assessment (PSA) scales
used in these RCTs. Both of these scales are based on subjective judgements and
not objective measures. However, considering the type of condition and the
intended use of the product (symptomatic reduction of erythema rather than
curative treatment), the EPAR states that these scales are sufficiently described
and validated for their intended purpose. The primary efficacy end point was a 2grade improvement on both the CEA and PSA over 12 hours. The authors of the
phase II studies (Fowler et al. 2012) stated that this was a stringent criterion for
success required for regulatory approval. They suggest a 1-grade improvement on
both CEA and PSA represents an effect that is noticeable by both investigators and
patients, and is therefore clinically relevant. However, specialists have
suggested that without further validation, defining what a clinically important
change is on these scales is difficult.
The European public assessment report for Mirvaso® states that the efficacy and
safety of brimonidine tartrate gel in people whose condition is being treated with
other topical products for rosacea, such as metronidazole or azelaic acid gel, has
not been systematically investigated. However, in the open-label, long-term study,
other rosacea treatments were allowed and although not large numbers, 70 people
used metronidazole gel and 27 used azelaic acid gel.
Page 7 of 12
Options for PAC
Option 1: To support the use of brimonidine tartrate gel in accordance with its
licensed indications.
Option 2: The use of brimonidine tartrate gel is not supported.
Option 3:.The use of brimonidine tartrate gel is supported for use in adults with a
clinical diagnosis of rosacea and moderate to severe erythema (marked or fiery
redness). Use should be restricted to days when patients feel that their appearance
is particularly important. Before continuing longer-term treatment with brimonidine
tartrate gel, consideration will need to be given to how treatment efficacy can be
assessed given the subjective nature of efficacy outcomes and the low response
rates seen in the clinical trials.
PAC New Drug Template – Adapted from East Anglia Medicines Information, NHS Suffolk, NHS
Cambridgeshire and NHS Derby templates
*Consult Summary of Prescribing Characteristics for full prescribing details.
This guidance is based upon the published information available in English at the time the drug was considered.
It remains open to review in the event of significant new evidence emerging.
References:1. Facial erythema of rosacea: Brimonidine tartrate, NICE new medicine summary, published 08
July 2014. http://www.nice.org.uk/Advice/ESNM43
2. The summary of product characteristics for Mirvaso®, Galderma International, 21 February
2014. http://www.medicines.org.uk/emc/medicine/28682#ORIGINAL (accessed 03/08/14)
3. Summary of Potential Financial Implications of New Drug Introductions for the 2014/15
Financial Year, produced by BCCG, February 2014
4. Brimonidine tartrate gel, New Drugs Online monograph.
http://www.ukmi.nhs.uk/applications/ndo/record_view.asp?newDrugID=5932
(Accessed 03/8/14)
5. Ivermectin, New Drugs Online monograph.
http://www.ukmi.nhs.uk/applications/ndo/record_view.asp?newDrugID=5617
(Accessed 03/08/14).
6. All Wales Medicines Strategy Group – Advice on brimonidine (Mirvaso®)
http://www.awmsg.org/awmsgonline/app/appraisalinfo/21686
(Accessed 03/08/14)
7. Ilkovitich D, Pomerantz RG. Case Letter: Brimonidine effective but may lead to significant
rebound erythema. Journal of the American Academy of Dermatology 2014; 70 (5): e109e110
H:\PAC work\Brimonidine Gel\PAC policy full review Bulletin Brimonidine tartrate gel for rosacea 150914_VG
CommentsJC response.docx
Appendix 1- Search Strategy
None undertaken as the review was based on a very recent NICE New Evidence Summary.
Page 8 of 12
Assessment against Ethical and Commissioning Principles
Treatment assessed (September 2014):
Brimonidine tartrate gel (Mirvaso®) for the symptomatic treatment of facial erythema of
rosacea in adult patients.
East of England Priorities Advisory Committee Recommendation

The use of brimonidine tartrate gel is not supported as it is considered to be a
cosmetic product.
1) Clinical Effectiveness
In 2 short-term randomised controlled trials (RCTs: n=553) brimonidine tartrate gel was
statistically significantly more effective than vehicle gel in reducing erythema in people with a
clinical diagnosis of rosacea and moderate to severe erythema. However, 'success rates'
(defined as a 2-grade reduction in the severity of erythema as assessed by both patients and
clinicians) were just 25% to 30% with brimonidine gel compared with about 10% for vehicle
gel at day 29.
2) Cost Effectiveness
No cost-effectiveness studies were identified.
If it is assumed that 50% of patients are eligible for treatment with brimonidine topical gel and
cost is £33/patient/month, this could result in an additional cost implication of ~£33,000 per
100,000 population. If usage is only 15g/patient per month, the additional cost implication
would be ~ £16,500 per 100,000 population.
3) Equity
No issues identified.
4) Needs of the community
Management of facial erythema of rosacea generally consists of lifestyle advice. Off-label
propranolol or clonidine may be used to treat flushing but this use is not supported by
evidence from RCTs. For persistent erythema or telangiectasia, laser therapy can be
effective although improvement is not permanent, and this may not be available on the
NHS. Camouflage cream is also used.
Mild or moderate papulopustular rosacea is usually treated with topical metronidazole or
azelaic acid. The activity of these drugs on underlying erythema and flushing is based
reduction of inflammatory redness and long term action on small vessels, but they provide
no immediate and evident improvement on baseline erythema that can be evident in the
short term.
For moderate or severe papulopustular rosacea, oral tetreacycline, erythromycin,
doxycycline or lymecycline can be prescribed, although not all of these drugs are licensed
for treating rosacea and RTC data to support their use are limited.
5) Need for healthcare (incorporates patient choice and exceptional
need)
Incidence rate for diagnosed rosacea in the UK is 1.65 per 1,000 person-years. Rosacea is
diagnosed in 80% of cases after the age of 30 years. Ocular symptoms are recorded in 21%
of cases.
6) Policy drivers
None
7) Disinvestment
None identified. It is likely that this treatment (if approved) would be used in addition to current
treatments.
Page 9 of 12
Grids used to assist the NHS Suffolk PCT Drug & Therapeutics Committee in reaching a decision about new medications
For many years scientists have recognised two types of research:
 Primary: original studies, based on observation or experimentation on subjects.
 Secondary: reviews of published research, drawing together the findings of two or more primary studies.
In biomedical science there is general agreement over a hierarchy: the higher up a methodology is ranked, the more robust and closer to objective truth it is
assumed to be. The orthodox hierarchy looks something like thisRank:
Methodology
Description
1
Systematic reviews and meta-analyses
Systematic review: review of a body of data that uses explicit methods to locate primary studies,
and explicit criteria to assess their quality.
Meta-analysis: A statistical analysis that combines or integrates the results of several
independent clinical trials considered by the analyst to be "combinable" usually to the level of reanalysing the original data, also sometimes called: pooling, quantitative synthesis.
Both are sometimes called "overviews."
Randomised controlled trials
(finer distinctions may be drawn within this
group based on statistical parameters like the
confidence intervals)
Individuals are randomly allocated to a control group and a group who receive a specific
intervention. Otherwise the two groups are identical for any significant variables. They are
followed up for specific end points.
3
Cohort studies
Groups of people are selected on the basis of their exposure to a particular agent and followed up
for specific outcomes.
4
Case-control studies
"Cases" with the condition are matched with "controls" without, and a retrospective analysis used
to look for differences between the two groups.
5
Cross sectional surveys
Survey or interview of a sample of the population of interest at one point in time
6
Case reports.
A report based on a single patient or subject; sometimes collected together into a short series
7
Expert opinion
A consensus of experience from the good and the great.
8
Anecdotal
Something a bloke told you after a meeting or in the bar.
2
Adapted from Systematic reviews, What are they and why are they useful? ScHARR 2008
Page 10 of 12
To Decide if a Medication Is To Be Used In Suffolk
Criterion to be measured
Quality of evidence in the papers reviewed
Magnitude of effect inferred from trials reviewed
Are trial end-points surrogate markers or clinical outcomes?
Clinical usefulness of trial end-points
Known Side Effect Profile
Known Interactions
Concern re Possible Side Effects Not Yet Uncovered
Balance of Benefit To Harm (side effects toxicity interactions etc)
NNT
Comparison Of Effectiveness With Other Medicines In Use For The
Same Condition
Severity of Condition to be Treated
Novel drug or member of existing class
Uptake (estimated proportion of people with this condition likely to be
prescribed the medication under consideration – maximum and
minimum uptake)
Is the drug to be used in Suffolk?
Tends to poor
7-8
Low
Low
5-6
Medium
3-4
Medium
Medium
2
Tends to good
1
High
High
Low
High
High
High
Poor
High
Poor
Medium
Medium
Medium
Medium
Medium
Medium
Medium
High
Low
Low
Low
Good
Low
Good
Severe
Medium
Trivial
Prescriber’s Rating Definitions
1. Bravo! -The drug is a major therapeutic advance in an area where previously no treatment was available.
2. A real advance - The product is an important therapeutic innovation but has certain limitations.
3. Offers an advantage - The product has some value but does not fundamentally change present therapeutic practice.
4. Possibly Helpful - The product has minimal additional value, and should not change prescribing habits except in rare circumstances.
5. Judgement reserved - The Committee postpones its judgement until better data and a more thorough evaluation of the drug are available.
6. Nothing New - The product may be a new substance but is superfluous because it does not add to the clinical possibilities offered by previous
products available. In most cases these are “me-too” products.
7. Not acceptable - Product without evident benefit over others but with potential or real disadvantages.
(With acknowledgement to Prescrire)
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To Decide Where A Medication Is To Be Used In Suffolk
Skills of the
prescriber
Therapy
Criterion
Experience Of The Condition
Red
Specific
Amber
Specific
Green
Specific
Blue
General
Diagnosis
Monitoring Progress Of Treatment
Specific
Difficult
Specific
Specific
Specific
General
General
General
Patient Selection
Initiation Of Treatment
Dose Titration
Monitoring Of Side Effects
Method Of Administration
Discontinuation Of Treatment
Difficult
Difficult
Difficult
Complex
Complex
Complex
Specific
Difficult
Specific
Easy
Normal
Complex
Specific
Easy
Easy
Easy
Normal
Easy
Easy
Easy
Easy
Easy
Normal
Easy
References
Jonsen A. Bentham in a box: Technology assessment and health care allocation. Law Med. Health Care. 1986;14:172-174
Suffolk Drug & Therapeutics Committee Responsibility for prescribing, Hospital Trust or GP Attached as Appendix 1 & Appendix 2
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