Salbutamol Sulfate, oral pressurised inhalation, 100 micrograms (base) per dose (200 doses), CFC-free formulation with spacer, VentSpacer®
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Product: SALBUTAMOL SULFATE, oral pressurised
inhalation, 100 micrograms (base) per dose (200 doses), CFC-free
formulation with spacer, VentSpacer®
Sponsor: Medical Developments International
Ltd
Date of PBAC Consideration: March 2010
1. Purpose of Application
To request PBS listing for salbutamol sulfate pressurised metered
dose inhaler (pMDI) (Ventolin®) with an asthma
spacer (Space Chamber®), packaged together in an
“Asthma Procedure Pack” (VentSpacer®) as
a Restricted Benefit for patients who are unable to achieve
coordinated use of other metered dose inhalers containing
salbutamol or patients at risk of an acute asthma episode.
2. Background
Ventolin brand of salbutamol sulfate pMDI 100 micrograms per dose
has been available on the PBS since 1972. An application for
listing of an asthma spacer device has not previously been
considered by the PBAC.
3. Registration Status
Ventolin Inhaler CFC-Free (salbutamol 100 microgram (as sulfate)
pMDI) was TGA registered on 30 June 1998 for the relief of
bronchospasm in patients with asthma or chronic obstructive
pulmonary disease, and for acute prophylaxis against
exercised-induced asthma and other stimuli known to induce
bronchospasm.
The Space Chamber asthma spacer was TGA registered as a Medical
Device Included Class 1 on 18 July 2007 with the following intended
purpose:
“a hand-held, portable device used to deliver aerosolized medication directly into the mouth of the user for delivery to the lungs”.
The VentSpacer Asthma Procedure Pack was TGA registered as a
Medical Device Included Class 1 on 8 December 2009 with the
following intended purpose:
“This pack contains an Aerosol Chamber to enhance the delivery of aerosolised medication from the included pressurised metered dose inhaler for enhanced delivery to the lungs”.
4. Listing Requested and PBAC’s View
Restricted Benefit
Patients who are:
- unable to achieve coordinated use of other metered dose inhalers containing salbutamol; or
- at risk of an acute asthma episode.
NOTE:
Patients should be restricted to one VentSpacer script per annum.
Should they lose or damage their spacer then another script for
VentSpacer may be provided. All other scripts of SALBUTAMOL SULFATE
oral pressurised inhalation 100 microgram (base) per dose (200
doses), CFC-free formulation should be delivered through a pack not
containing an asthma spacer.
The PBAC considered that the requested restriction for patients at
risk of an acute asthma episode would in practice include all
patients with asthma. The PBAC considered that the note associated
with the requested listing restricting to one VentSpacer per annum
per patient via a restricted benefit listing was unrealistic and
may be clinically inappropriate.
The PBAC’s view was that the submission raised a number of
policy issues, including whether the PBS was the most appropriate
mechanism for the subsidy of spacer devices. The PBAC also noted
that the submission requested the listing of one brand of spacer
with one brand of salbutamol inhaler.
5. Clinical Place for the Proposed Therapy
Australian clinical guidelines recommend the use of spacers by
adults with poor coordination when using a pMDI, by children of all
ages, and during an acute asthma attack. Spacer devices hold the
aerosol cloud produced from pMDIs in a confined space, and allow
subsequent inhalation. They have a valve system, which can assist
drug delivery in patients who have problems coordinating actuation
of the pMDI and inhalation. They are effective in decreasing the
oropharyngeal deposition of medication and increasing the relative
dose delivered to the lungs. The submission stated that listing of
salbutamol delivered via a spacer on the PBS would reduce the price
to the consumer, and with the delivery of a quality use of medicine
(QUM) program, would improve awareness and clinical use of asthma
spacers.
6. Comparator
The submission nominated salbutamol sulfate pressurised inhalation
in breath actuated device (Airomir Autohaler®) as
the comparator for patients unable to achieve coordinated use of
other metered dose inhalers containing salbutamol. The submission
nominated salbutamol nebules or nebuliser solution administered via
nebuliser as the comparator for patients at risk of an acute asthma
episode. The PBAC noted that the appropriate comparator was not
clear but did not consider delivery of salbutamol using alternate
delivery systems was appropriate.
7. Clinical Trials
One randomised, placebo-controlled, cross-over trial (Giannini
2000) which compared pMDI, pMDI plus spacer (Volumatic) and
breath-activated Autohaler in stable moderate asthma; and one
Cochrane review (Cates 2006, updated in 2008) which compared beta-2
agonists delivered by MDI plus spacer (any type) versus delivery by
a nebuliser in acute asthma were presented by the submission. None
of the studies included the Space Chamber used in the VentSpacer
Procedure Pack.
Trial ID / First author | Protocol title / Publication title | Publication citation |
Giannini D, et al. (2000) | The protective effect of salbutamol inhaled using different devices on metacholine bronchoconstriction. | Chest 2000; 117:1319-1323. |
Cates CJ, et al. (2006) | Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. | Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD000052. DOI:10.1002/14651858.CD000052.pub2. |
8. Results of Trials
In the Giannini (2000) study there was no statistically significant
difference in provocative dose of methacholine inducing a 20% fall
in the forced expiratory volume in one second (FEV1) or
change in FEV1 between pMDI plus Volumatic spacer and
Autohaler. The PBAC noted that Giannini (2000) was a small study
and was not powered to demonstrate non-inferiority. The clinical
relevance of the outcome from this study was considered uncertain
by the PBAC.
In the Cates (2006) review, there were no statistically significant
differences between delivery via pMDI plus spacer versus nebuliser
in acute asthma in a range of outcomes including hospital
admissions, duration in Emergency Departments (ED) (adults only),
final rise in FEV1, 30 minutes rise in FEV1,
final FEV1 rise in severe asthmatics and final risk in
peak flow. The only statistically significant difference was
observed for duration in ED in children, favouring pMDI plus
spacer. The Cochrane review concluded that MDIs with spacer were at
least equivalent to nebuliser therapy. The Cochrane review
presented relates to the treatment of acute asthma attack not for
the treatment of chronic asthma which is the population primarily
targeted with the requested listing. The PBAC noted that the Space
Chamber was not used in any of these studies. No clear evidence was
available which showed that the treatment effect was improved by
one particular kind of spacer.
The submission did not present any safety information specific to
the use of the Space Chamber or the proposed combination
product.
9. Clinical Claim
The submission described the proposed product as non-inferior in
terms of comparative effectiveness and safety over Airomir
Autohaler and nebuliser. The Space Chamber was not used in any of
the studies presented. The submission’s claims rest on
inferences that all spacer devices are equally effective.
10. Economic Analysis
The submission presented three cost comparison analyses and
reported that there were cost-savings in all three cases. The
comparison with Airomir Autohaler relied on the assumption that
only one VentSpacer pack was prescribed per year.
The PBAC considered that the cost saving approach presented in the
submission is highly unlikely to eventuate in practice as patients
who currently achieve the desired health outcome using the
autohaler are unlikely to switch to the pMDI with spacer if it were
to be listed.
11. Estimated PBS Usage and Financial Implications
The likely number of patients treated with VentSpacer per year were
estimated to be between 10,000 and 50,000 in Year 1 of listing,
rising to between 100,000 and 200,000 in Year 5 of listing and the
net financial cost per year (less patient co-payments) to the PBS
was < $10 million in Year 5.
12. Recommendation and Reasons
The PBAC considered that the requested restriction for patients at
risk of an acute asthma episode would in practice include all
patients with asthma. The PBAC considered that the note associated
with the requested listing restricting to one VentSpacer per annum
per patient via a restricted benefit listing was unrealistic and
may be clinically inappropriate. There is no mechanism available to
restrict prescribing of an item on the PBS to once per year via a
restricted benefit listing. Additionally, the PBAC noted that the
Asthma Management Handbook 2006 recommends that spacers be replaced
at least every 12 months, and that additional spacers could
appropriately be prescribed should the patient lose their spacer.
The PBAC also noted that prescribers and patients may wish to
obtain more than one spacer to use in various locations, such as at
home and at school. Further, the PBAC noted that should an
authority required listing be considered, the volume of authority
requests would be high and would result in a substantial increase
in authority applications to Medicare Australia.
In relation to the other part of the requested restriction for
patients unable to achieve coordinated use of other metered dose
inhalers containing salbutamol, the PBAC noted that the VentSpacer
product contains Ventolin brand salbutamol inhaler only, rather
than the spacer component of VentSpacer being available with any
PBS listed salbutamol inhaler.
In relation to the patient population for which listing was
requested, the PBAC noted that the Cochrane review (Cates et. al.
2006) which compared beta-2 agonists delivered by metered dose
inhaler (MDI) plus a spacer (various types) versus delivery by a
nebuliser in acute asthma was not representative of the target
patient population requested, as the Cochrane review relates to the
treatment of acute asthma attack, rather than the treatment of
chronic asthma (patients at risk of an asthma attack) which was the
population primarily intended with the requested listing.
The submission nominated salbutamol sulfate pressurised inhalation
in breath actuated device (Airomir Autohaler) as the comparator for
patients unable to achieve coordinated use of other metered dose
inhalers containing salbutamol and salbutamol nebules or nebuliser
solution administered via nebuliser as the comparator for patients
at risk of an acute asthma episode. The PBAC agreed with ESC that
the appropriate comparator is not clear but did not consider
delivery of salbutamol using alternate delivery systems was
appropriate.
The PBAC noted the submission presented one randomised,
placebo-controlled, cross-over trial (Giannini 2000) which compared
pressurised metered dose inhaler (pMDI) (Ventolin brand), pMDI plus
spacer (Volumatic brand) and breath-activated pMDI (Autohaler
brand) in stable moderate asthma. The results of the study showed
no statistically significant difference in a provocative dose of
methacholine inducing a 20 % fall in forced expiratory volume in
one second (FEV1) or change in FEV1 between
the pMDI plus Volumatic spacer and the Autohaler. The PBAC noted
that Giannini was a very small trial with only 18 subjects and that
the study was not powered to demonstrate non-inferiority.
Importantly the PBAC noted that the Space Chamber spacer contained
in VentSpacer was not used in the Giannini study. For these reasons
the PBAC considered that the clinical relevance of the outcome of
Giannini was uncertain.
The PBAC noted the Cochrane review (Cates 2006) also did not use
the Space Chamber spacer and that the Cochrane review did not
provide evidence that the treatment effect is improved by any one
particular kind of spacer. The Cochrane review found that in
treatment of acute asthma attack there was no statistically
significant differences observed between delivery via pMDI plus
spacer versus nebuliser in acute asthma measured by a range of
outcomes.
The PBAC noted the submission did not present any safety
information specific to the use of the Space Chamber or
VentSpacer.
The PBAC noted that the submission presented three cost comparison
analyses based on the assumption of VentSpacer being of equivalent
clinical effectiveness and safety to the nominated comparators. The
PBAC noted that the cost comparison analysis to Airomir Autohaler
relied on the assumption that only one VentSpacer pack would be
prescribed per year. The PBAC considered this to be uncertain
considering the restriction issues noted above (inability in the
requested restriction to limit prescribing to one VentSpacer per
year and the appropriateness of limiting to one per year) and that
the cost saving claim is unlikely to eventuate in practice as
patients who currently achieve the desired health outcome using an
autohaler are unlikely to switch to the pMDI with spacer if it were
to be listed.
The PBAC noted the submission reported that the requested price of
$38.60 for VentSpacer is slightly lower than the cost of purchasing
the components separately ($41.82). However, the PBAC noted that
there are other spacers available that are less expensive than the
price of $26.60 used for the Space Chamber in the submission and
that other brands of salbutamol MDIs are also available at a lower
price than the price of $15.22 used in the submission. The PBAC
considered that no evidence was presented in the submission to
substantiate the significant price premium requested for the Space
Chamber spacer component of VentSpacer over other spacers currently
available on the market.
The PBAC considered that the utilisation of VentSpacer was
uncertain. The PBAC noted that there would be the potential for use
beyond the proposed restriction such as prescribing for patients
with other respiratory conditions, for example chronic obstructive
pulmonary disease. The PBAC also noted that it is likely that in
some instances more than one spacer would be prescribed in a period
of 12 months. The PBAC also considered that there is the
possibility that spacers currently provided in other places, such
as emergency departments of public hospitals, and bought over the
counter at pharmacies would be switched to provision through the
PBS.
The PBAC recognised that spacers have an important place in the
treatment of asthma and that the use of spacers is supported by
Australian practice guidelines. However the PBAC considered that
the submission failed to present sufficient evidence to show that a
health benefit to patients or society would result from subsidising
VentSpacer via the PBS, or that an improvement in the quality use
of medicines in asthma would result from the listing. The PBAC
considered that there are some barriers to affordable access to
asthma spacers in the Australian community; however the submission
did not present any information on potential gaps in access to
spacer devices to provide evidence of a clinical need for the PBS
subsidy of spacers in Australia. The PBAC was uncertain if
providing PBS subsidised spacers would assist with acknowledged
gaps in quality use of medicine in asthma such as the lack of use
of spacers even in those patients who currently own a spacer.
The PBAC noted that the submission raised a number of policy
issues, including whether the PBS was the most appropriate
mechanism for the subsidy of spacer devices. The PBAC also noted
that the submission requested the listing of one brand of spacer
with one brand of salbutamol inhaler. The PBAC noted that spacers
are also used with other medications besides salbutamol in the
treatment of asthma, such as with inhaled corticosteroids. Should a
spacer device be recommended for listing on the PBS it was
uncertain if it was appropriate to restrict supply to the
combination with one drug and/ or brand of inhaler.
Therefore the PBAC recommended rejection of the submission on the
basis of uncertain clinical and uncertain cost effectiveness.
The PBAC noted that the submission meets criteria for independent
review.
Recommendation:
Reject
13. Context for Decision
The PBAC helps decide whether and, if so, how medicines should be
subsidised in Australia. It considers submissions in this context.
A PBAC decision not to recommend listing or not to recommend
changing a listing does not represent a final PBAC view about the
merits of the medicine. A company can resubmit to the PBAC or seek
independent review of the PBAC decision.
14. Sponsor’s Comment
The sponsor would like to continue to work with the PBAC to determine the best pathway for this important product to be made available to asthma patients through the Pharmaceutical Benefits Scheme.