Product: Sensura Mio One-Piece Closed Flat Pouch s1

PUBLIC SUMMARY DOCUMENT

Product: SenSura Mio One-Piece Closed Flat Pouch Applicant: Coloplast Pty Ltd Date of SPAP Meeting: 29-30 July 2013

1. Proposed Listing on the Stoma Appliance Scheme The applicant, Coloplast, sought the addition of a price premium to a product currently listed in Subgroup 1(b) of the SAS Schedule, the SenSura Mio One-Piece Closed Flat Pouch (SAS code 5697W). The applicant proposed a unit price inclusive of a price premium over the benchmark unit price for Subgroup 1(b) ($2.735).

The price premium requested was for: 1. ‘The ability of the SenSura Mio elastic double layer baseplate to improve skin condition and reduce usage of accessories. 2. Abilities of SenSura Mio to improve aspects related to quality of life, valued by utilisation of willingness-to-pay.’

2. Comparator The applicant nominated a ConvaTec product listed in Subgroup 1(b) of the SAS Schedule, the Esteem One-Piece Closed Flat Pouch (SAS code 3806H), as the comparator. This product is currently listed at the benchmark unit price of $2.735.

3. Background An application requesting a unit price premium (higher than the unit price premium applied to this product from the date of first listing on 21 November 2011) was considered by the Stoma Product Assessment Panel (SPAP) in November 2012 as part of the Group 1 Price Premium Review (SAS 2012-13 Budget measure). At that time the SPAP recommended the removal of the existing price premium on the basis of insufficient evidence for its justification – a recommendation that received Cabinet approval in February 2013 and came into effect on 1 April 2013.

4. Clinical Place for the Product The product is a one-piece closed appliance with a flat baseplate suitable for use by people with a colostomy.

5. SPAP Comment

Clinical Analysis The applicant’s claim of the superiority of the SenSura Mio product (as distinct from the SenSura range) was based on the presence of an elastic adhesive in the double layer baseplate, which, it claimed, allows for physical activity and is better able to mould to different body shapes. In support of the claim of superiority, the applicant presented two main studies and a lab test of elasticity. The studies were CP209OC (comparator product Coloplast SenSura One-Piece Closed Flat Pouch) and CP219OC (comparator products a ‘standard of care’ consisting of Coloplast SenSura, ConvaTec Esteem, Dansac Nova 1, Hollister ModermaFlex and Omnigon B Braun Flexima/Softima one-piece closed flat pouches).

CT#1 Study CP209OC, a three-week (10-12 days per phase), open label, cross-over, randomised controlled trial involving 54 subjects in France and Denmark, had a primary endpoint of leakage – assessed after any change and measured on a four-point scale. Secondary endpoints included comfort, feeling of security, handling, pain on removal, patient preference, safety, skin condition, sports activity and wear time. Subjects were colostomates of at least three months who were currently using a one-piece closed flat appliance. Importantly, the presence of peristomal skin conditions (PSCs) and/or any steroidal treatment of PSCs in the three weeks preceding the commencement of the study constituted exclusion criteria.

Results of CP209OC were as follows:  leakage: 70% of change episodes for both products were reported as ‘no leakage’. There appeared to be no difference between the two products and non-inferiority was stated by the applicant;  comfort: 92.6% of patients reported the test product as ‘comfortable’ or ‘very comfortable’ versus 66.6% for the reference product – a statistically significant difference. It was noted that there was a significant period effect here, with subjects who used the Mio product first rating the comfort of the SenSura product lower than did subjects who used the SenSura product first. This would tend to indicate that subjects were discerning and differentiating between the two products. The measure of how often patients were reminded of wearing a stoma bag was less for the test product;  detachment: there was no significant difference between the two products;  feeling of security: 48.1% reported as ‘very good’ for the test product versus 27.8% for the reference product. The percentage recording ‘acceptable’ or above was 87% for both products;  handling: there was no difference between the two products;  pain on removal: there was no significant difference between the two products;  patient preference: 77% preferred the test product.  skin condition: there was no statistical difference between the two products;  sports activity: patient ratings of the products’ ability to follow movements of the body favoured the test product. It was noted that more patients did exercise during the Mio testing phase; and  wear time: there was no significant difference between the two products.

The Panel noted that there was no difference observed in study CP209OC in the primary endpoint of leakage, and that if the product fitted better during exercise then less leakage would have been an expected observation. It was noted that all other outcome measures were subjective and subject to confounding. Those endpoints which had some component of objectivity – for example detachment, handling, skin condition and wear time – showed no significant difference between the test and reference products. The Panel noted that a significant proportion of subjects preferred the Mio to the SenSura product, a result possibly related to perceived comfort and security. Finally the Panel noted that this study compared two SenSura products (one a Mio) and that no comparative data was presented with reference to the selected comparator.

Study CP219OC, a four-week (two weeks per phase), open label, cross-over, randomised controlled trial involving 122 subjects, had a primary endpoint of leakage (measured on a

CT#1 25-point scale). Secondary endpoints included leakage (measured on a four-point scale), skin condition based on DET (discolouration, erosion and tissue overgrowth) score, the ability of the adhesive to fit around the stoma and follow movements of the body, feeling of security, patient preference, the reason for change, the use of accessories and wear time.

Results of CP219OC were as follows:  leakage (25-point scale): there was no difference between the two products in terms of the percentage of baseplates recording leakage underneath. The mean score was statistically higher for the test product (3.8 versus 3.4) but this was unlikely to be clinically significant;  leakage (four-point scale): statistically less for the reference group than for the test product – for example 53% recorded ‘no leakage’ under the baseplate for the test product versus 58% for the reference group;  skin condition: there was a difference of 0.22 in the change in DET scores (measured at inclusion, cross-over and final visit) between the subjects using the test product versus those using a reference group product, which on a scale of 0-15 – with 0-4 equating to a mild PSC – was unlikely to be clinically significant. It was noted that the percentage breakdown of the presence before and after both test phases of the various types of PSCs (allergic contact dermatitis, irritant-contact dermatitis, disease and trauma) contained no measure of severity (mild, moderate or severe), which had implications for its subsequent use as an input into the applicant’s economic modelling. The only borderline clinically relevant result contained within this breakdown was the difference in mechanical trauma rates (2.63% for the test product versus 9.73% for the reference group of products);  the ability of the adhesive to fit around the stoma/follow movements of the body: patient ratings on a five-point scale were better on both counts for the test product (4.0 and 4.1 respectively) than for the reference group (3.7 and 3.8 respectively). While these differences were statistically significant they were unlikely to be clinically relevant, and the Panel considered that the nature of the questions and the open label nature of the trial were likely to have resulted in confounding of results on this endpoint;  feeling of security: there was no difference between the test product and the reference group of products;  patient preference: 69% preferred the test product versus 31% for the reference group of products;  the use of accessories: there was no overall difference between the test product and the reference group of products; and  wear time: there was no overall difference between the test product and the reference group of products.

With regard to study CP219OC, the Panel noted that the technique of grouping the five ‘standard care’ products together to form a reference group would have suppressed any differences present between individual products. The assumption that all five products were the same with regard to all outcomes was highly likely to have been incorrect (the Panel noted for example that one of the five products – the Hollister ModermaFlex – contained the AF300 filter for which a price premium has previously been granted). The lack of a breakdown of outcomes by product makes the generalisability of results uncertain, as any one of the products may have dominated the (reference) results. As for study CP209OC, the Panel also considered the subjective nature of the outcome measures to be a limitation.

CT#1 In relation to both CP209OC and CP219OC, the Panel noted that short-term cross-over studies without any wash-out period between the cross-over are highly susceptible to carryover effects, especially when dealing with conditions such as PSCs which may take three to four weeks to resolve given optimum treatment.

In support of the claim of greater baseplate elasticity, the applicant presented the results of a lab test of ‘E modulus’, a test of stretch versus load where a smaller E modulus corresponds to greater polymer elasticity and flexibility. E modulus was smaller for the SenSura Mio product than for the nine other products tested, but how that would extrapolate into clinically-relevant outcomes was considered to be uncertain. In particular, the Panel noted that it was inconsistent with the principal results of studies CP209OC and CP219OC, where no difference in leakage between test and reference products was observed (and in fact point estimates favoured the comparator group in the latter study). As previously stated, the Panel considered results regarding the ability of the adhesive to fit around the stoma and follow movements of the body to be subject to confounding arising from the open label nature of the trial and the subjective nature of the outcome measures.

The applicant provided additional supporting evidence with regard to filter performance. Study CP201OC, a four-week (two weeks per phase), open label, cross-over, randomised controlled trial involving 48 subjects, had a primary endpoint of ballooning. Secondary endpoints included general filter dysfunction, filter lifetime (time to ballooning), filter discretion and patient preference. Subjects were colostomates using a closed system who prior to the study had experienced ballooning at least once per week. The products tested were all SenSura products containing either the old ‘Wave’ filter or the new SenSura filter design. It was noted that the relevance of this study to the current submission depends on the assumption that the SenSura Mio One-Piece Closed Flat Pouch is fitted with the new filter.

Results of CP201OC were as follows:  ballooning rates per day were 0.35 for the test products versus 0.49 for the reference products, equating to a 29% reduction in ballooning rates in favour of the test products. It was noted that this was not extrapolated into any patient-relevant outcomes;  filter dysfunction (leakage, odour and pancaking): the mean values for events were not clinically (or statistically) different between the two product groups;  filter lifetime: time to ballooning was also reduced for the test products by comparison with the reference products;  filter discretion: similar results seen for both product groups; and  patient preference: similar results seen for both product groups.

The second piece of data was provided by the Coloplast Laboratory Test, an in-vitro test measuring air flow. Results were as follows:  air flow through the Hollister AF300 filter was almost double that of the SenSura filters (both old and new designs) at the start;  following one artificial contamination cycle the air flow through the test and both comparator products (the Hollister AF300 and the old SenSura ‘Wave’ filter) was the same; and  following subsequent contamination cycles the new SenSura filter outperformed both comparator products.

CT#1 The Panel noted these results, however in the absence of an in-vitro/in-vivo correlation or a head-to-head study of the in-vivo performance of a product containing the new SenSura filter versus a comparator containing the AF300 filter, interpretation of the results was uncertain.

Finally, the Panel noted with reference to the overarching submission that the Hollister ModermaFlex One-Piece Closed Flat Pouch, which has previously been awarded a unit price premium of $0.274 for the AF300 filter, may have been a more appropriate comparator to nominate had the applicant wished to address the issue of filter performance as a formal basis of the claim for a price premium.

Economic Analysis The Panel noted that although the applicant stated that the data used in the economic modelling was derived from study CP219OC, the approach used was the same as that of the six other Coloplast submissions under consideration at this meeting. As with these other submissions, the analysis had three main components: a base case model based on the treatment costs associated with PSCs, a reduction in accessory use and ‘willingness to pay.’ An arbitrary discounting approach was applied by the applicant to each in an attempt to address perceived areas of uncertainty within the economic modelling.

With regard to the PSC component of the applicant’s economic case, it was noted by the Panel that the average cost of treating any particular skin condition was taken from the other Coloplast submissions, which use PSC data from the Dialogue Study which are categorised by severity. In this submission the cost is simply taken to be the average of the cost of managing mild, moderate and severe PSCs and is not weighted in any way by the proportion of patients falling within the different categories of severity (as previously stated, no evidence is provided to indicate that severity was measured in trial CP219OC). This submission is also unique in that the applicant increased the number of nurse and specialist visits assumed to be required by a proportion of patients to four and four respectively within a period of two weeks (cf. seven weeks in the other submissions), resulting in increased cost estimates.

Given that the net financial impact of PSCs in terms of treatment costs is highly dependent upon the distribution between severity categories, the offsets claimed by the applicant were considered to be highly uncertain and likely to be biased towards the applicant’s product (ie. overestimated).

With regard to accessory usage, the Panel noted that the groups using the test and reference products in study CP219OC recorded very similar overall usage. It was also noted that in calculating this component of the unit price premium, the applicant only included offsets based on point estimates which favour the test product, while accessory usage results favouring comparator products were omitted. The submission ignores, for example, the increases in ‘mouldable rings, ostomy tape or other [accessories]’ which are greater for the test product, and also fails to identify the 16% versus 8% usage of ‘Other’ accessories which favour the comparators. As such, the data used to support the claim of a reduction in accessory usage associated with the product was selective and incomplete, an approach which the Panel considered to be unacceptable. This component of the unit price premium calculation was therefore also considered to be highly uncertain and biased towards the applicant’s product.

CT#1 In calculating the component of the per unit price premium based on willingness to pay, the applicant took as a starting point the attribute of comfort and flexibility, added a component for (a non-statistical difference in) episodes of skin problems and made claims regarding wear time (based on filter lifetime) where no difference in this outcome was recorded in study CP219OC. The calculated incremental value based on willingness to pay was not based on quality of life, which was not measured in CP219OC, but on small differences in performance measured in a poorly-designed study and valued by an unpublished study which used different metrics. These issues, together with other concerns regarding willingness to pay (in particular the possible double counting of benefits related to skin condition across the three categories of economic analysis), also made this component of the per unit price premium claim highly uncertain in the view of the Panel.

Financial Analysis Not undertaken.

Overarching Summary of SPAP Position This submission sought a price premium greater than that currently offered to products listed with a premium in the same subgroup.

The evidence base failed to address the performance of the product against an appropriate comparator and there were serious methodological errors as well as evidence of selective reporting.

The two pivotal trials, CP209OC and CP219OC, each had too short a study period and permitted carry-over effects at cross-over that were unknown and have not been adequately accounted for. Neither study provided the applicant with any basis to argue the case of product superiority based on the pre-specified primary endpoint (leakage).

The issue of the filter is problematic. Products containing the AF300 filter have been granted a premium on the basis of greater air flow at time zero, less ballooning and patient preference over the SenSura product (old ‘Wave’ filter). The applicant has presented data indicating greater air flow of the new SenSura filter after artificial contamination over both the old SenSura filter and the AF300. Data is also presented that ballooning is reduced by 29% comparing the old and new SenSura filters, which the applicant argues validates the in- vitro contamination data. However an in-vivo comparison between the new SenSura filter and the AF300 is not presented and it is unknown whether the reduction seen between the two products over the common comparator (the SenSura Wave) would be different. The AF300 data submitted in 2011 also demonstrated a greater gas deodorising capacity. In essence, while there may be a benefit of the new SenSura filter over the old SenSura filter, the quantification and monetary value of that benefit is highly uncertain and its comparison with the AF300 filter is unknown.

There is therefore no basis provided within the current submission for the granting of a premium over the base-priced products in the subgroup.

6. SPAP Recommendation The SPAP recommended that the applicant’s request for the application of a unit price premium to the SenSura Mio One-Piece Closed Flat Pouch (SAS code 5697W), currently listed in Subgroup 1(b) of the SAS Schedule, be rejected due to an inadequate evidence base in support of the claim of product superiority.

7. Context for Decision

CT#1 The SPAP helps decide whether stoma products should be subsidised and, if so, the conditions of their subsidisation in Australia. It considers submissions in this context. An SPAP decision not to recommend listing or not to recommend changes to a listing does not represent a final SPAP view about the merits of a particular stoma product. A company can resubmit to the SPAP following a decision not to recommend listing or changes to a listing. The SPAP is an advisory committee and as such its recommendations are non-binding on Government. All SPAP recommendations are subject to Cabinet/Ministerial approval.

8. Applicant’s Comment There were no comments provided in relation to the SPAP recommendation.