4 Consideration of the evidence

4.1 The Appraisal Committee reviewed the data available on the clinical and cost effectiveness of pixantrone, having considered evidence on the nature of multiply relapsed or refractory non-Hodgkin's B‑cell lymphoma and the value placed on the benefits of pixantrone by people with the condition, those who represent them, and clinical specialists. It also took into account the effective use of NHS resources.

4.2 The Committee discussed the treatment pathway for multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma. It heard from the clinical specialists that rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone (also known as R‑CHOP) was the standard first-line treatment in England and Wales, and that most patients would also receive a rituximab-containing regimen second line. If their disease did not relapse within 6 months of first-line treatment, patients would be treated with rituximab. The Committee also noted that the clinical specialists stated that people treated with rituximab were less likely to respond to any subsequent treatment. The Committee heard that a platinum-based regimen was offered as second-line treatment but that there was no consensus on third- or fourth-line treatment. The Committee heard from the clinical specialists and the patient expert that the aim of treatment at this disease stage was to reduce the impact of symptoms on quality of life, as well as extending life, and could include chemotherapy or participating in clinical trials. The clinical specialists highlighted that fifth-line options include palliative care or participating in clinical trials. The Committee also noted that the marketing authorisation states that the benefit of pixantrone treatment has not been established in patients when used as fifth-line or further chemotherapy in patients whose disease is refractory to last therapy.

4.3 The Committee heard from the patient expert about the impact of multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma on daily life and that the symptoms of the disease can reduce quality of life. It heard that patients are normally told at the start of their treatment that they are being treated with curative intent and that experiencing multiple relapses can be devastating; consequently, they would value any new treatment that could offer symptom relief, have a positive impact on quality of life and increase survival. The Committee acknowledged the demands that living with multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma can place on patients and accepted that a treatment option for these patients is important.

Clinical effectiveness

4.4 The Committee reviewed the suitability of the clinical trial evidence submitted by the manufacturer and expressed several concerns about the PIX301 trial. It considered PIX301 to be underpowered because it had failed to recruit the planned number of patients. It also noted that European regulators prefer a primary end point of overall survival or progression-free survival for clinical trials of anticancer drugs, but the primary end point for PIX301 was complete or unconfirmed complete response. The Committee heard from the clinical specialists that although this end point would have been acceptable when the trial began in 2004, positron emission tomography (PET) scans have made unconfirmed complete response obsolete in trials that have begun more recently. The Committee also heard from the clinical specialists that they considered studies that were powered to detect a difference in overall survival to be more useful for clinical decision-making. The Committee concluded that these fundamental concerns about the design of PIX301 meant that there was considerable uncertainty in the validity and robustness of its results.

4.5 The Committee discussed the relationship between the marketing authorisation, the PIX301 population and clinical practice in England and Wales. The Committee was aware that the intention-to-treat population included around 10% of patients who did not have aggressive B‑cell lymphoma, making them ineligible for treatment with pixantrone according to the terms of the marketing authorisation. The Committee further noted that the marketing authorisation is for multiply relapsed or refractory disease (that is, it is approved for patients who have received at least 2 previous lines of treatment) and that this does not necessarily restrict its use to third- and fourth-line treatment. However, it also noted the comments received during consultation stating that patients receiving fifth-line or further treatment would likely have palliative treatment or participate in a clinical trial. The Committee was persuaded that pixantrone would most likely be used, within its marketing authorisation, as a third- or fourth-line treatment in clinical practice in England and Wales. The Committee concluded that, when assessing the PIX301 results, it would be more appropriate to consider the population with aggressive B‑cell lymphoma who had received third- or fourth-line treatment.

4.6 The Committee discussed how the tumour histologies were determined in the PIX301 population and whether this was generalisable to clinical practice in England and Wales. It was aware that tumour histology in the intention-to-treat population of PIX301 had been determined by onsite review by a single pathologist. The Committee heard from the clinical specialists that this was not representative of clinical practice in England and Wales, in which multidisciplinary team review is routine and specimens are examined by 2 or 3 pathologists. It noted that the Evidence Review Group (ERG) had also been advised by clinical specialists that a population with disease confirmed by central independent pathological review was more relevant to clinical practice in England and Wales. It also noted that a considerable proportion of patients were excluded after the central independent pathological review (for example, if indolent disease had been confirmed). The Committee concluded that it would be more appropriate to consider the PIX301 population with tumour histology confirmed by retrospective central independent pathological review by consensus than by onsite review by a single pathologist.

4.7 The Committee discussed whether the comparator arm (treatment of physician's choice) in PIX301 was relevant to clinical practice in England and Wales. It heard from clinical specialists that, apart from PIX301, there was no evidence base for selecting a third- or fourth-line treatment for multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma and that there was wide variation in the treatments used in clinical practice in England and Wales. The Committee concluded that all of the comparators used in the treatment of physician's choice arm in PIX301 were clinically relevant (although there was some uncertainty in the proportions in PIX301 compared with clinical practice in England and Wales), and the comparator arm was therefore acceptable for decision-making.

4.8 The Committee discussed the generalisability of previous treatments received by the PIX301 population to clinical practice in England and Wales. The Committee heard from the clinical specialists that rituximab is an integral part of standard first-line treatment in the NHS and is also often used as a second-line treatment. The Committee noted that the manufacturer's subgroup analyses showed a reduced benefit of pixantrone in patients who had previously received rituximab, and that many of the results showed no statistically significant difference between treatment arms (see sections 3.11 and 3.16–3.18). It also noted a clinical specialist's concern that statistical significance was not reached for the parameters complete or unconfirmed complete response, progression-free survival and overall survival for this subgroup. The Committee accepted the non statistically significant results because of the positive trend in all 3 outcomes for this subgroup. It was aware from comments received during consultation that this reduced benefit applied to other drugs in clinical development and was not specific to pixantrone. It was also aware of the obligation to the European Medicines Agency in pixantrone's European marketing authorisation requiring a trial to confirm the clinical benefit in patients who have previously received rituximab. However, the Committee acknowledged the comments received in response to consultation that the complete response rates with pixantrone in PIX301 were among the highest reported to date in trials for patients with diffuse large B‑cell lymphoma who had previously received rituximab. The Committee concluded that it was appropriate to evaluate the subgroup of patients in PIX301 who had previously received rituximab because this would apply to almost all patients with multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma in England and Wales.

4.9 The Committee considered the clinical-effectiveness results for the whole intention-to-treat trial population and all the post-hoc subgroups. It noted that in the intention-to-treat population, PIX301 was inadequately powered to detect a difference between treatment groups because it had accrued less than half of the planned 320 patients. It noted that the difference in response rates, progression-free survival and overall survival between treatment groups did not always reach statistical significance in the intention-to-treat population (see section 3.17) and the post-hoc subgroups, and that there was no statistically significant difference in overall survival between treatment arms for any groups presented by the manufacturer. The Committee had reservations about whether superior efficacy of pixantrone had been shown for the intention-to-treat trial population.

4.10 The Committee then discussed the clinical effectiveness for the subgroup of patients it considered to be most appropriate for decision making (those receiving third- or fourth-line treatment and who had previously received rituximab [see section 3.18]). It concluded that there was an increase in response rates, progression-free survival, and overall survival for pixantrone compared with treatment of physician's choice, and that the mean survival advantage of pixantrone compared with treatment of physician's choice was 2.0 months. However, these results were not statistically significant (see section 3.18). The Committee also concluded that there was limited and non-robust evidence to show that pixantrone was more clinically effective than treatments currently used in the Committee's preferred subgroup.

4.11 The Committee discussed the adverse events associated with pixantrone. It noted the manufacturer's assertion that pixantrone was associated with less cardiotoxicity than anthracyclines. The Committee was aware that the final scope issued by NICE did not include any anthracyclines as comparators and that mitoxantrone was the only anthracenedione out of the 6 comparators. It heard from clinical specialists that doxorubicin (an anthracycline) was used as first-line treatment, and that none of the comparators for third- or fourth-line treatment were associated with the similarly raised cardiovascular risk associated with anthracyclines. The Committee was aware that there were more cardiac adverse events in the pixantrone group than in the comparator group, who received treatment of physician's choice (35% compared with 21%). However, it heard from the clinical specialists that efficacy is considered key in this patient population and that, because of its cardiovascular safety profile compared with anthracyclines, pixantrone offered an opportunity for response in patients who had previously shown sensitivity to anthracyclines but who could not receive further lines of anthracycline treatment after relapse because they had reached the maximum lifetime dose. It concluded that pixantrone had an acceptable adverse-effect profile although it was associated with more cardiotoxicity than treatments such as oxaliplatin and gemcitabine that are routinely used in this population in clinical practice in England and Wales.

Cost effectiveness

4.12 The Committee discussed the manufacturer's general approach to developing the submitted pixantrone economic models. It noted that the ERG considered the manufacturer's approach to follow current best practice and was largely transparent. The Committee concluded that the outlined structure of the models adhered to the NICE reference case for economic analysis and was acceptable for assessing the cost effectiveness of pixantrone.

4.13 The Committee considered the manufacturer's cost-effectiveness analyses that included the patient access scheme for the Committee's preferred patient subgroup (that is, the subgroup with aggressive B‑cell lymphoma confirmed by central independent pathological review for third- or fourth-line treatment and who had previously received rituximab [see section 4.10]). In particular the Committee discussed how quality of life had been incorporated into the manufacturer's economic modelling. It was aware that the base-case analysis in the manufacturer's patient access scheme submitted in November 2013 used utility values for patients receiving second- and subsequent-line treatment for renal cell carcinoma (0.76 for the pre-progression health state and 0.68 for the post-progression health state). It noted the absence of published utility values in the relevant patient population and that the manufacturer intends to fund additional research in this area. The Committee noted that the utility value for the pre-progression health state (0.76) was similar to that expected for a healthy older population in the UK, and it considered that the quality of life of patients receiving third- or fourth-line treatment for aggressive non-Hodgkin's B‑cell lymphoma could be lower than this. The Committee then reviewed the utility values selected by the ERG for its exploratory analyses using the manufacturer's original model and the revised model supplied with the patient access scheme submission, which were for patients receiving final-line treatment for chronic lymphocytic leukaemia (0.428 for the pre-progression health state and 0.279 for the post-progression health state). The Committee heard from the clinical specialists that there were differences between the 2 conditions that could mean these utility values were too low, and decided that the ERG's utility values were likely to underestimate the quality of life for this population. Having excluded the ERG's low utility values, the Committee considered that the manufacturer's deterministic sensitivity analysis on the base case in the patient access scheme submission using various utility values (see section 3.37) showed that utility values were not a key driver of cost effectiveness. The Committee concluded that, although there was some uncertainty as to the true utility value, the utility values used in the manufacturer's revised model with the patient access scheme were acceptable for use in the Committee's decision-making.

4.14 The Committee considered the incremental cost-effectiveness ratios (ICERs) and considered those presented in the manufacturer's most recent cost-effectiveness analyses, which included the patient access scheme for the Committee's preferred patient subgroup. For the comparison of pixantrone with treatment of physician's choice, it noted that the manufacturer's deterministic and mean probabilistic ICERs incorporating the patient access scheme for this population were £18,500 and £22,000 per quality-adjusted life year (QALY) gained respectively. The Committee noted that the ERG had validated the changes made to the manufacturer's model as part of the patient access scheme submission in November 2013. The Committee concluded that the manufacturer's analysis was appropriate for its decision-making.

4.15 The Committee discussed the amount of uncertainty in the cost-effectiveness estimates for the Committee's preferred subgroup of patients, that is people with aggressive B‑cell lymphoma confirmed by central pathological review receiving third- or fourth-line treatment and who have previously received rituximab. The Committee was persuaded that the manufacturer's mean probabilistic ICER of £22,000 per QALY gained could overestimate the uncertainty associated with the survival modelling and that the true value of the ICER might be lower. It was aware that the median probabilistic ICER was £14,700 per QALY gained and that the probabilistic ICER reduced to £10,000 per QALY gained when assuming that progression-free survival and overall survival did not change independently of each other. The Committee noted that the manufacturer's exploratory probabilistic sensitivity analysis showed that the probability of pixantrone being cost effective compared with treatment of physician's choice was 56% at a maximum acceptable ICER of £30,000 per QALY gained, and approximately 50% at a maximum acceptable ICER of £20,000 per QALY gained. Additionally, although pixantrone was less clinically effective in 32% of simulations, it was less expensive than treatment of physician's choice in a high proportion of these at a maximum acceptable ICER of £20,000 per QALY gained. The Committee therefore agreed that the probability of pixantrone being cost-effective compared with treatment of physician's choice was acceptable. The Committee concluded that the most plausible ICER was likely to be less than £22,000 per QALY gained, and it concluded that pixantrone was recommended as a cost-effective use of NHS resources.

4.16 The Committee discussed whether pixantrone was innovative in its potential to make a significant and substantial impact on health-related benefits. It observed that pixantrone is the first drug that has been tested in a randomised phase III trial in patients with multiply relapsed or refractory aggressive non-Hodgkin's lymphoma. It examined whether pixantrone had the potential to make a significant and substantial impact on health-related benefits but heard from the clinical specialists that it was uncertain whether pixantrone could be considered a step change in treatment. On the basis of currently available evidence, the Committee did not consider pixantrone to be a step change in managing multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma. The Committee observed that there were no additional gains in health-related quality of life over those already included in the QALY calculations. The Committee concluded that there were no additional QALYs that had not been incorporated into the economic model and the cost-effectiveness estimates.

4.17 The Committee understood that pixantrone's conditional marketing authorisation is linked to results from the ongoing PIX306 study, which should be available in 2015. It noted that this larger randomised phase III study (n=350) will compare the effectiveness of pixantrone plus rituximab with gemcitabine plus rituximab in patients with relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma who have already received a rituximab-containing regimen. Given the relevance of the patient population (because virtually all patients with multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma in England and Wales will have previously received rituximab [see section 4.8]), the Committee recommended that the technology appraisal guidance on pixantrone for treating multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma should be considered for review by NICE once the PIX306 results are available in 2015.

4.18 The Committee considered whether NICE's duties under the equality legislation required it to alter or to add to its recommendations. It noted that no equality issues had been raised during scoping, in any of the consultees' submissions, during consultation or during the Committee meetings. The Committee concluded that its decision on the use of pixantrone does not have a particular impact on any group with a protected characteristic in the equality legislation and that there was no need to alter or add to its recommendations.

Summary of Appraisal Committee's key conclusions

TA306

Appraisal title: Pixantrone monotherapy for treating multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma

Section

Key conclusion

Pixantrone monotherapy is recommended as an option for treating adults with multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma only if:

  • the person has previously been treated with rituximab and

  • the person is receiving third- or fourth-line treatment and

  • the manufacturer provides pixantrone with the discount agreed in the patient access scheme.

The Committee concluded that there was limited and non-robust evidence to show that pixantrone was more clinically effective than treatments currently used in clinical practice for treating multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma. It further concluded that there was an increase in response rates, progression-free survival, and overall survival for pixantrone compared with treatment of physician's choice. However, these results were not statistically significant.

The Committee noted that using the revised model that incorporated the patient access scheme, the manufacturer's deterministic ICER was £18,500 per quality-adjusted life year (QALY) gained and that the mean probabilistic ICER was £22,000 per QALY gained. The Committee agreed that the probability of pixantrone being cost effective compared with treatment of physician's choice was acceptable and that the most plausible ICER was likely to be less than £22,000 per QALY gained. It therefore concluded that pixantrone could be recommended as a cost-effective use of NHS resources.

1.1, 3.18, 4.8, 4.9, 4.10, 4.14, 4.15

Current practice

Clinical need of patients, including the availability of alternative treatments

The Committee heard from the clinical specialists and the patient expert that the aim of treatment at this disease stage was to reduce the impact of symptoms on quality of life, as well as extending life, and could include chemotherapy and participating in clinical trials. The Committee heard from the patient expert that patients would value any new treatment that could offer symptom relief, have a positive impact on quality of life and increase survival. The Committee acknowledged the demands that living with multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma can place on patients and accepted that a treatment option for these patients is important.

4.2, 4.3

The technology

Proposed benefits of the technology

How innovative is the technology in its potential to make a significant and substantial impact on health-related benefits?

Pixantrone (Pixuvri, Cell Therapeutics) is an aza‑anthracenedione analogue and inhibitor of topoisomerase II. The Committee concluded that there was limited and non-robust evidence to show that pixantrone was more clinically effective than treatments currently used in clinical practice to treat multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma. It further concluded that there was an increase in response rates, progression-free survival, and overall survival for pixantrone compared with treatment of physician's choice. However, these results were not statistically significant.

The Committee examined whether pixantrone had the potential to make a significant and substantial impact on health-related benefits. On the basis of currently available evidence, the Committee concluded that using pixantrone would not be a step change in managing multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma and that there were no additional QALYs that had not been incorporated into the economic model and the cost-effectiveness estimates.

2.1, 4.8, 4.9, 4.10, 4.18

What is the position of the treatment in the pathway of care for the condition?

Pixantrone has a conditional marketing authorisation 'as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin B‑cell lymphomas (NHL). The benefit of pixantrone treatment has not been established in patients when used as fifth line or greater chemotherapy in patients who are refractory to last therapy'.

In light of consultee and commentator responses to consultation, the Committee considered that it was appropriate to restrict its assessment of pixantrone to third- and fourth-line treatment. The Committee concluded that the subgroup in PIX301 with aggressive B‑cell lymphoma confirmed by central independent pathological review receiving third- or fourth-line treatment and who had previously received rituximab was the most appropriate for decision-making.

2.1, 4.5, 4.8, 4.9, 4.10

Adverse reactions

The summary of product characteristics states that the most common toxicity with pixantrone is bone marrow suppression (particularly the neutrophil lineage) and that other toxicities such as nausea, vomiting and diarrhoea are generally infrequent, mild, reversible, manageable and as expected in patients treated with cytotoxic agents. Although the occurrence of cardiac toxicity indicated by congestive heart failure appears to be lower than that expected with related drugs like anthracyclines, the summary of product characteristics recommends monitoring left ventricular ejection fraction.

The Committee concluded that pixantrone had an acceptable adverse-event profile although it was associated with more cardiotoxicity than treatments such as oxaliplatin and gemcitabine that are routinely used in this population in clinical practice in England and Wales.

2.2, 4.11

Evidence for clinical effectiveness

Availability, nature and quality of evidence

The Committee considered that the PIX301 trial was underpowered because it had failed to recruit the planned number of patients. It also noted that European regulators prefer a primary end point of overall survival or progression-free survival for clinical trials of anticancer drugs, but the primary end point for PIX301 was complete or unconfirmed complete response. The Committee considered that although the PIX301 study had included a high proportion of patients who would be eligible for treatment under the terms of the marketing authorisation, the intention-to-treat population was not appropriate for evaluation and decision-making. The Committee concluded that these fundamental concerns about the design of PIX301 meant that there was considerable uncertainty in the validity and robustness of its results.

4.4, 4.5

Relevance to general clinical practice in the NHS

Because tumour specimens would be examined by 2 or 3 pathologists in clinical practice in England and Wales, the Committee concluded that it would be more appropriate to consider results from the PIX301 trial using a population with tumour histology confirmed by retrospective central independent pathological review by consensus than by onsite review by a single pathologist.

4.6

Uncertainties generated by the evidence

The Committee was concerned that only just over half of patients in the PIX301 trial had previously received rituximab because it heard from the clinical specialists that rituximab is an integral part of standard first-line treatment in the NHS and also often used as a second-line treatment. It was aware of the obligation to the European Medicines Agency in pixantrone's marketing authorisation requiring a trial to confirm the clinical benefit in patients who have previously received rituximab. The Committee noted a reduced benefit of pixantrone in the subgroup of patients who had previously received rituximab, but concluded that it was appropriate to evaluate this subgroup because this would apply to almost all patients with multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma in England and Wales.

4.8, 4.19

Are there any clinically relevant subgroups for which there is evidence of differential effectiveness?

The Committee was aware that the intention-to-treat population included patients whose tumour histology would make them ineligible for treatment with pixantrone according to the terms of the European marketing authorisation. The Committee concluded that the subgroup of patients in PIX301 with aggressive B‑cell lymphoma confirmed by central independent pathological review receiving third- or fourth-line treatment and who had previously received rituximab was the most appropriate for decision-making.

4.5, 4.9, 4.10

Estimate of the size of the clinical effectiveness including strength of supporting evidence

The Committee concluded that for the subgroup of patients it considered to be most appropriate for decision making (those receiving third- or fourth-line treatment and who had previously received rituximab) there was an increase in response rates, progression-free survival, and overall survival for pixantrone compared with treatment of physician's choice, and that the mean survival advantage of pixantrone compared with treatment of physician's choice was 2.0 months. However, these results were not statistically significant. The Committee concluded that there was limited and non-robust evidence to show pixantrone was more clinically effective than treatments currently used in clinical practice for treating multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma.

4.9, 4.10

Evidence for cost effectiveness

Availability and nature of evidence

The Committee concluded that the outlined structure of the models adhered to the NICE reference case for economic analysis and was acceptable for assessing the cost effectiveness of pixantrone.

4.12

Uncertainties around and plausibility of assumptions and inputs in the economic model

The Committee was persuaded that the manufacturer's mean probabilistic ICER of £22,000 per QALY gained could overestimate the uncertainty associated with the survival modelling and that the true value of the ICER might be lower. It further concluded that there was an increase in response rates, progression-free survival, and overall survival for pixantrone compared with treatment of physician's choice. However, these results were not statistically significant.

4.9, 4.10, 4.15

Incorporation of health-related quality-of-life benefits and utility values

Have any potential significant and substantial health-related benefits been identified that were not included in the economic model, and how have they been considered?

The Committee was aware that the utility value used by the manufacturer in its revised model incorporating the patient access scheme for the pre-progression health state was similar to that expected for an older population in the UK. The Committee considered that the quality of life of patients receiving third- or fourth-line treatment for aggressive non-Hodgkin's B‑cell lymphoma could be lower than this. The Committee concluded that, although there was some uncertainty as to the true utility value, the utility values used in the manufacturer's revised model that was part of the patient access scheme submission were appropriate for use in the Committee's decision-making. The Committee observed that there were no additional gains in health-related quality of life over those already included in the QALY calculations and concluded that there were no additional QALYs that had not been incorporated into the economic model and the cost-effectiveness estimates.

4.13, 4.18

Are there specific groups of people for whom the technology is particularly cost effective?

The patient access scheme applies to patients with histologically confirmed aggressive non-Hodgkin's B‑cell lymphoma who have previously received rituximab and are receiving pixantrone as a third- or fourth-line treatment.

3.34–3.38

What are the key drivers of cost effectiveness?

The Committee concluded that there was limited and non-robust evidence to show pixantrone was more clinically effective than treatments currently used in clinical practice for treating multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma. It further concluded that there was an increase in response rates, progression-free survival, and overall survival for pixantrone compared with treatment of physician's choice. However, these results were not statistically significant.

The patient access scheme reduced the mean probabilistic ICER to £22,000 per QALY gained. The Committee was persuaded that this ICER could overestimate the uncertainty associated with the survival modelling and that the true value of the ICER might be lower.

4.10, 4.14, 4.15

Most likely cost-effectiveness estimate (given as an ICER)

The Committee noted that, for the subgroup of patients with aggressive B‑cell lymphoma confirmed by central independent pathological review for third- or fourth-line treatment and who had previously received rituximab, the manufacturer's deterministic ICER incorporating the patient access scheme was £18,500 per QALY gained and the manufacturer's mean probabilistic ICER was £22,000 per QALY gained. The Committee noted that the exploratory analysis showed a high level of uncertainty around the ICER. However, the Committee was persuaded that this analysis could overestimate the uncertainty associated with the survival modelling and that the true value of the ICER might be lower. The Committee concluded that because the probabilistic ICER was likely to be less than £22,000 per QALY gained pixantrone was recommended as a cost-effective use of NHS resources.

4.14, 4.15

Additional factors taken into account

Patient access schemes (PPRS)

The manufacturer of pixantrone has agreed a patient access scheme with the Department of Health that makes pixantrone available with a discount. The size of the discount is commercial in confidence. The Department of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS.

2.3

End-of-life considerations

Not appropriate.

4.16, 4.17

Equalities considerations and social value judgements

The Committee concluded that its decision on the use of pixantrone does not have a particular impact on any group with a protected characteristic in the equality legislation and that there was no need to alter or add to its recommendations.

4.20