Macrogol 3350, sachet containing 13.125 g powder, 30, Movicol®, March 2007
Public summary document for Macrogol 3350, sachet containing 13.125 g powder, 30, Movicol®, March 2007
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Public Summary Document
Product: Macrogol 3350, sachet containing 13.125 g
powder, 30, Movicol®
Sponsor: Norgine Pty Ltd
Date of PBAC Consideration: March 2007
1. Purpose of Application
The submission sought an extension to the current restricted
benefit listing to include the treatment of patients with chronic
constipation due to neurogenic causes not responding to other oral
therapies.
2. Background
At the June 2002 PBAC meeting, macrogol 3350 (13.125 g, sachet) was
recommended for a restricted benefit listing for the treatment of
constipation in patients with malignant neoplasia, on the basis of
acceptable cost-effectiveness compared to lactulose. PBS listing
was implemented on 1 November 2002.
At the November 2005 PBAC meeting the Committee considered a
request for an extension to the current listing to include the
treatment of faecal impaction in adults, where conventional
therapies have failed, and the alternative treatments may require
hospitalisation; and to request a similar listing for a lower
strength product (Movicol Half) that can be used in adults and
children for the treatment of faecal impaction, where conventional
therapies have failed, and the alternative treatments may require
hospitalisation. The PBAC rejected the submission because of
clinical and economic uncertainties and inadequately demonstrated
cost-effectiveness.
3. Registration Status
Macrogol 3350 is registered on the ARTG for effective relief from
constipation and treatment of chronic constipation. Macrogol 3350
is also effective in resolving faecal impaction, defined as
refractory constipation with faecal loading of the rectum and/or
colon confirmed by physical examination of the abdomen and
rectum.
4. Listing Requested and PBAC’s View
Restricted benefit
Paraplegic and quadriplegic patients and others with severe
neurogenic impairment of bowel function not responding to other
oral therapies.
See Recommendation and Reasons for the PBAC’s
view
5. Clinical Place for the Proposed Therapy
The listing of macrogol 3350 would provide patients with neurogenic
causes of constipation access to an osmotic therapy if unresponsive
to other oral treatments.
6. Comparator
The submission nominated rectal interventions such as suppositories
and enemas as appropriate comparators.
7. Clinical Trials
The submission presented results from four randomised comparative
studies of macrogol 3350 in chronic constipation as primary
evidence. The submission also presented six non-comparative studies
and one before-and-after study of macrogol 3350 in chronic
constipation as supportive evidence. There were no trials comparing
macrogol with the submissions chosen comparator, rectal
interventions.
These trials had been published at the time of submission, as
follows:
| Trial/First author | Protocol title/Publication title | Publication citation |
| Attar A et al, 1999 | Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for treatment of chronic constipation. | Gut 1999; 44(2): 226–30. |
| Attar A et al, 1996 | A randomized study comparing a low-dose polyethylene glycol solution (PEG) 3350 and lactulose in chronic idiopathic constipation. | Gastroenterologie Clinique et Biologique 1996; 20: A21. |
| Eichhorn TE et al | Macrogol 3350/electrolyte improves constipation in Parkinson's disease and multiple system atrophy. | Movement Disorders 2001; 16(6): 1176–7. |
| Gruss H-J et al | Treatment of chronic constipation. Results of a multi-centre observation period on the use of polyethylene glycol 3350 plus electrolytes. | Der Allgemeinarzt 1999; 21:1342–1350. |
| Gruss H-J et al | Efficacy and tolerability of PEG 3350 plus electrolytes (Movicol) in chronic constipation associated with Parkinson’s disease. | European Journal of Geriatrics 2004; 6:143–149. |
| Kalke YB et al. | Study to assess the efficacy, safety and tolerability of Macrogol 3350 plus electrolytes (Movicol) to manage the treatment of bowel dysfunction in patients with spinal cord injuries/disease. | Annual congress of the German-Speaking Medical Society for Paraplegia (DMGP). 2002 |
| Lemann M et al | Efficacy of low dose polyethylene glycol (PEG) 3350 (Movicol) in idiopathic constipation: double blind crossover study against placebo. | Gastroenterol Clin Biol 1994 ; 18: B256. |
| Mingeon-Duballet I et al | Long-term efficacy and cost-effectiveness of polyethylene glycol 3350 plus electrolytes in chronic constipation: a retrospective study in a disabled population. | Current Medical Research and Opinion 2006; 22: P1-P9 |
| Schlosser A et al | The use of Movicol in the treatment of severe, treatment-refractory constipation in the intellectually disabled. | Medical Aspects of Mental Handicap Conference, June 1998. |
| Wang HJ et al, 2004 | A randomised, controlled comparison of low-dose polyethylene glycol 3350 plus electrolytes with ispaghula husk in the treatment of adults with chronic functional constipation. | Clin Drug Invest 2004; 24: 556–579. |
| Wang HJ et al, 2005 | A randomised, controlled comparison of low-dose polyethylene glycol 3350 plus electrolytes with ispaghula husk in the treatment of adults with chronic functional constipation. | Drugs in R&D 2005; 6 (4): 221–5. |
| Wang HJ et al, 2002 | Efficacy and safety of polyethylene glycol 3350 in the treatment of human functional chronic constipation. | Chinese Journal of New Drugs 2002; 11: 483–486. |
8. Results of Trials
Given that the majority of evidence presented by the submission was not trial outcomes,
and the submission did not consistently provide the results of statistical analyses,
it was difficult to draw definitive conclusions regarding the efficacy of macrogol.
In its calculation of the outcomes presented for the ‘primary evidence’ macrogol trials,
the submission calculated ‘best’ and ‘worst’ case scenarios. In the ‘best case’ scenario
for a beneficial outcome, all discontinued patients were assumed to be successful,
except those specifically noted as treatment failures, and were added to those patients
defined as having a positive response. In the worst case scenario for a beneficial
outcome all discontinued patients were assumed to have failed treatment. The opposite
was used for detrimental outcomes.
The results of the selected ‘primary evidence’ macrogol trials, as presented by the
submission, are summarised in the table below:
| Trial | Timepoint | Proportion with 3 stools/wk | Proportion using suppository/enema | ||
| Worst case a | Best case b | Worst case c | Best case d | ||
| Attar | |||||
| macrogol | baseline 4 weeks | 6/60 (10%) 45/60 (75%) | 6/60 (10%) 53/60 (88.3%) | NR 17/60 (28.3%) | NR 7/60 (11.7%) |
| lactulose | baseline 4 weeks | 9/55 (16.4%) 42/55 (76.4%) | 9/55 (16.4%) 46/55 (83.6%) | NR 23/55 (41.8%) | NR 17/55 (30.9%) |
| Lemann | |||||
| macrogol | baseline 2 weeks | NR 28/39 (71.8%) | NR 35/39 (89.7%) | NR 11/39 (28.2%) | NR 4/39 (10.3%) |
| placebo | baseline 2 weeks | NR 18/39 (46.2%) | NR 25/39 (64.1%) | NR 22/39 (56.4%) | NR 15/39 (38.5%) |
| MOV-PARK | |||||
| macrogol | baseline 3 weeks | 0/3 (0%) 3/3 (100%) | - - | - - | - - |
| lactulose | baseline 3 weeks | 3/6 (50%) 4/6 (66.7%) | - - | - - | - - |
| Wang | |||||
| macrogol | baseline 2 weeks | 0/63 (0%) 50/63 (79.4%) | 0/63 (0%) 58/63 (92.1%) | - - | - - |
| ispaghula husk | baseline 2 weeks | 0/63 (0%) 26/63 (41.3%) | 0/63 (0%) 46/63 (73%) | - - | - - |
NR=not reported
a all discontinued patients were assumed to have failed treatment
b all discontinued patients were assumed to be successful, except those specifically
noted as treatment failures, and were added to those patients defined as having a
positive response
c all discontinued patients were assumed to have used suppositories or enemas
b all discontinued patients were assumed to have not used suppositories or enemas
The pooled results presented by the submission were merely proportions from each included
trial added together. Given that the trials pooled together were of different design,
included different patient populations and compared different outcomes across the
macrogol and rectal intervention trials, it was difficult to draw definitive conclusions
about the comparative efficacy of macrogol and rectal interventions.
9. Clinical Claim
The submission claimed that macrogol 3350 had a similar efficacy to
rectal interventions, but had greater effectiveness (i.e. a greater
number of patients were willing to use macrogol 3350).
See Recommendation and Reasons for PBAC’s
view.
10. Economic Analysis
A preliminary economic evaluation using a cost-effectiveness
approach and including only drug costs was presented.
A modelled economic evaluation was presented.
11. Estimated PBS Usage and Financial Implications
The submission estimated that the likely number of patients treated
with macrogol per year would be < 10,000 in Year 3 of listing
while the financial cost per year to the PBS, after accounting for
the savings from the reduced number of rectal interventions, would
be < $10 million per year in Year 3.
12. Recommendation and Reasons
The PBAC considered that the evidence presented in the submission
to be poor and unconvincing and acknowledged the difficulties
associated with collecting data in this patient group. Despite
this, the PBAC recognised that access to macrogol 3350 by this
patient group would meet an important clinical need, that
superiority over other oral therapies had been more convincingly
demonstrated in other conditions impairing bowel function to a
similar extent sufficient to justify the price advantage for
macrogol 3350 over these other oral therapies and recommended
listing on this basis at the price requested.
The PBAC also suggested that the sponsor consider submitting an
application in the future to change the listing to an unrestricted
benefit.
Recommendation
MACROGOL 3350, sachet containing 13.125 g powder, 30,
Add the following to the restriction:
Restricted benefit
Paraplegic and quadriplegic patients and others with severe
neurogenic impairment of bowel function not responding to other
oral therapies.
Maximum Quantity: 1
Repeats: 5
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 chose not to make a comment.
